Q1 2021 X4 Pharmaceuticals Inc Earnings Call

[music].

Greetings and welcome to export Pharmaceuticals, first 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 to ask a question. During the session. You will meet the press star one on your telephone as the reminder of this conference call is being recorded.

Operator: Welcome to X4 Pharmaceuticals' first quarter financial and operating results conference call. At this time, while participants are in a listen-only mode, a question-and-answer session will follow the formal presentation. To ask a question during the session, you'll need to press Star 1 on your telephone. As a reminder, this conference call is being recorded. If you require any further assistance, please press Star Zero. It is now my pleasure to introduce your host, Dan Ferry, of Lifeside Advisors. Please begin. Thank you, operator. Thank you. Good morning, everyone. Thanks for joining us.

If you require any further assistance. Please press star zero. It is now my pleasure to introduce your host Dan theory of life side Visors. Please begin.

Daniel Ferry: Presenting on today's call will be X-For as Chief Executive Officer, Dr. Paul Reagan, and the company's chief financial officer, Adam Mustafa. Following prepared remarks by each, we will open the call to your questions. And we'll be joined by Dr. Diego Cade, Chief Medical Officer; Art Tavares, chief scientific officer; 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.

Daniel Ferry: as well as research activities. However, these statements are subject to risks and uncertainties that may cause actual results to differ.

Daniel Ferry: actual results to differ from those forecasts. A description of these risks can be found in X4's most recent filings with the SCC. I would now like to turn the call over to Paula Reagan. Paula?

The X force most recent filings with the SEC.

I would now like to turn the call over to Paul Reagan Paula.

Paula Ragan: Thanks, Dan, and thank you everyone for joining us on the call this morning. Let me start by saying that we could not be more pleased with our accomplishments so far this year. We have achieved significant progress in our Mavericksforic clinical programs and successfully completed a $55 million at the market pipe financing to include participation from leading biotech investors, both new to X4 as well as from existing investors. We believe this demonstrates a strong level of investor conviction and the clinical and commercial potential of Mavericks before, while also extending our expected cash runway into late 2022 and supporting our additional pipeline programs.

Thanks, Dan and thank you everyone for joining us on the call of morning, let.

Let me start by saying that we could not be more pleased with our accomplishments so far this year.

We've achieved significant progress and our Mavericks for clinical programs and successfully completed a $55 million at the market pipe financing to included participation from leading biotech investors, both new to X four as well as from existing investors.

We believe this demonstrates a strong level of of investor conviction, and the clinical and commercial potential of Mavericks before I'll also extending are expected cash runway until late 2022 and supporting our additional pipeline programs.

Paula Ragan: As mentioned on our last call, the pace of enrollment in our key clinical programs has ramped up significantly since last year. Specifically, we now expect to be able to announce an important enrollment update in our Phase 3 trial and WIM syndrome in mid-2020. As a reminder, WIM is a rare inherited primary immunodeficiency disease caused by gain of function CXCR4 mutations that prevent healthy immune cell trafficking and effective immunosurveill

As mentioned on our last call the piece of of enrollment Anarchy clinical programs has ramped up significantly since last year.

Specifically, we now expect to be able to announce an important enrollment update and our faith free trial and whim syndrome in mid 2021.

As a reminder, whim as of rare inherited primary immunodeficiency disease caused by gain of function C X P. R for mutations that prevent healthy immune so I'll trafficking and effective surveillance.

Most patients with the wind disease have lifelong neutropenia and Lymphopenia. The can result in a variety of serious chronic infections across multiple Oregon systems, HPV associated lesions and increased cancer risk and other serious lights impacting morbidities.

Maverick before as our first in class small molecule antagonist of the <unk> of receptor that we believe has the potential to be the first disease modifying therapy for the more than 3500 potential diagnosed and undiagnosed when patients in the U S.

Paula Ragan: Most patients with Wim disease have lifelong neutropenia and lymphopenia that can result in a variety of serious chronic infections across multiple organ systems, HPV-associated lesions and increased cancer risk, and other serious life-impacting morbidities. Mavericksifor is our first in-class small molecule antagonist of the CXDR4 receptor that we believe has the potential to be the first disease-modifying therapy for the more than 3,500 potential The four-whim phase three trial is a global, randomized, placebo-controlled, double-blinded, multi-center study designed to evaluate the safety and efficacy of Mavericks A four over the course of 52 weeks in approximately 18 to 28 genetically confirmed WIM patients.

The four O M faith free trial is a global randomized placebo controlled double blinded multicenter study designed to evaluate the safety and efficacy of Mavericks before over of course of 52 weeks in approximately 18 to 28 genetically confirmed when patients.

Paula Ragan: The phase three primary efficacy endpoint, called time above threshold for absolute neutrophil count (TAT ANC), compares the level of circulating neutrophils relative to a clinically meaningful threshold in response to Mavericks for treatment versus placebo. As you may recall from our Phase 2 study published in the journal Blood in 2020, Mavericks demonstrated greater than a 600% increase in time above threshold for Nutrafil counts at our selected Phase 3 dose as compared to the lower doses used for WIM patients, which gives us deep confidence in the potential success of our Phase 3 study. Secondary endpoints include infection rates, warp burden, and assessment of immune system function and quality of life, among others.

Weighted to of recently received notice of acceptance of our phase one b trial abstract for a poster presentation at this year's annual Congress of the European Hematology Association or E. H, a that would be taking place virtually from June 9th to June 17th the abstracts.

And poster will focus on initial clinical data from the ongoing phase one b trial of Maverick before at the study is low and mid doses in combination with Ibrutinib in the subset of Walden from macro globular anemia patients harboring both the N Y D. Eight eight <unk> four of mutations.

Paula Ragan: At our current rate of enrollment, we continue to expect top-line data from this phase three trial in 2022. We also continue to expect to report new data from the open-label extension of our Phase 2 clinical trial and WIM later this year. We expect these data will continue to provide us insights regarding the long-term safety and durability of chronic mavericks for treatment. Additionally, we anticipate several scientific publications that further support Mavericks or its Mechanism of Action and Potential for Disease Modification, as well as demonstrate its breadth of activity across the spectrum of when genotypes.

In addition to safety pharmacokinetics and Pharmacodynamic markers. The initial dataset will evaluate changes in serum immunoglobulin M or IGN and blood hemoglobin levels.

It is well established that reductions in IGN level and increases in hemoglobin levels correlate favorably with clinical responses for the treatment and Walden from patients.

Later this year, we expect that the study will mature further such that we should be able to prevent datasets regarding the determination of the final dose selection for further study and assessment of major response rates as well as ongoing safety across the range of doses.

Paula Ragan: Finally, we look forward to sharing new information regarding our additional WIME prevalence research later this year. In addition to our WIMP program, we continue to make good progress in our Phase 1B trial for the treatment of Waldstrom's macroglobulinemia, a rare form of non-Hodganslum phoma. As a reminder, this Phase 1B study is a multi-center, open-label, dose escalation clinical trial that is expected to enroll approximately 12 to 18 patients. We are very excited to have recently received notice of acceptance of our Phase 1B trial abstract for a poster presentation at this year's annual Congress of the European Hematology Association, or EHA, that will be taking place virtually from June 9th to June 17th.

Dollars from the first quarter of 2021 as compared to of net loss of $11.1 million for the first quarter of 2020.

Paula Ragan: The abstract and poster will focus on initial clinical data from the ongoing phase 1b trial of Mavericks-4 at the study's low and mid-doses in combination with abrutinib and the subset of Waldenstrom's macroglobulinemia patients harboring both the NYD-88 and CXR4 mutations. In addition to safety, pharmacokinetic, and pharmacodynamic markers, the initial data set will evaluate changes in serum It is well established that reductions in IGM levels and increases in hemoglobin levels correlate favorably with clinical responses to treatment in Waldemstrom's patients.

Note that net loss included in $1.3 million of certain non-cash expenses for the first quarter of 2021.

Why don't we know open up the call to your questions.

Operator.

Thank you.

As a reminder to ask a question you'll need to press the star one on your telephone.

The dry your question on press the pound cake. Please stay on violence of compile the Q&A roster.

Our first question comes from Stephen what Willy with sequels. The May I proceed with your question.

Yeah. Good morning, Thanks for taking the questions.

Paula was maybe wondering if you can just kind of frame up expectations of little bit with respect to.

I guess, what kind of day to we might see in the abstract when that gets released I think it's next week.

And I guess, how that may differ from what we could see it it sounds like you said, specifically that will be seeing.

Data from the law with mid doses have have you dose escalated patients up to that 600, Meg dose yet per of the S per the escalation protocol.

Paula Ragan: Later this year, we expect that the study will mature further such that we should be able to present data sets regarding the determination of the final dose selection for further study and assessment of major response rates, as well as ongoing safety across a range of doses. So, as you can see, 2021 has been quite productive for us to date, and we're looking forward to a steady flow of value-adding data presentations and business milestones throughout the rest of the year.

Yeah, I'll I'll try to break it all down free T. Then thank you so much of the question so.

The the way to think about walton's from that the disease is obviously the the heavy burden of IGN level, Inc. Definitely high, causing a lot of rest of the person who cares to call a like hyper of with coffee and drowned and then that massive bone disease burden from the cancer, the cloud, causing hemoglobin impac.

Though.

Or a patient you Wanna see I G M dropping in hemoglobin rising as a function of of being treated so that's really the focus of R. E. I data in terms of demonstrating changes in the IGN level and hemoglobin levels that can be indicative of the combination doing better than of Britain of alone he'll really be.

Paula Ragan: With that update, I will now turn the call over to Adam to discuss our results for the quarter and our recent financing announcements. 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 first quarter ended March 31, 2021. As of March 31, 2021, X4 had $116.7 million in cash, cash equivalence, and restricted cash.

Adam S. Mostafa: This figure includes proceeds from the pipe financing that we completed in mid-March. Through this at-the-market deal, we raised a gross amount of $55 million, with the financing including participation from a number of new and existing leading healthcare investors. After the close of this transaction, we now expect our cash and cash equivalence to fund company operations into the fourth quarter of 2022. Our research and development expenses were $12.1 million for the first quarter of 2021, as compared to $8.9 million for the comparable period in 2020.

Through 600, so the last cohort b is a bit rounding out the total number of patients.

So just stay tuned on that.

Understood and then just lastly.

Just curious as to where things stand on severe congenital neutropenia, which I don't think it was part of your prepared commentary or if it was on mute Mr.

Adam S. Mostafa: General and administrative expenses were $5.8 million for the first quarter of 2021, as compared to $4.7 million for the comparable period in 2020. And we reported a net loss of $18.7 million for the first quarter of 2021, as compared to a net loss of $11.1 million for the first quarter of 2020. Note that the net loss included $1.3 million of certain non-cash expenses for the first quarter of 2021.

Yeah no. Thank you so the Afghan trial is open and enrolling.

In the context of the COVID-19, especially last year on early this year. It was the most challenging study to enroll given that the short dosing timeframe. These patients are of immuno compromised. The study of two weeks. So we have always tried to prioritize the patient safety and their need to come into the hospitals for assessments. We do expect to have some initial data by the end of this year.

Here, but just in terms of patient numbers.

What we've guided to is a smaller number of patients spend obviously the total trial design. The look forward to sharing what we're able to towards the end of the year.

Understood. Thanks for taking the questions and congrats on the progress.

Thank you so much.

Yeah.

Thank you. Our next question comes from Mark from Cowen You May proceed with your question.

Thanks for taking my questions and congrats on the all the progress across the multiple programs.

Paul can you just remind us of the different doses in the Washington trial, just the kind of relative levels of CX, three or four inhibition that youre that youre expecting based on kind of all of the prior work you've done with the molecule.

Operator: Why don't we open up the call to your question now, operator? Thank you. As a reminder, to ask a question, you'll need to press Star 1 on your telephone. To withdraw your question, press the pound key.

Sure actually I would invite art various to pay its share of that he sent me a on one of our resident experts in exposure on inhibition So art.

Yes, hi.

And thank you for the question. So the exposures that we're going after all of our consistent with what we've seen from our phase II trial. So the doses. They are of course of the 200 400, and then ultimately 600.

Operator: Please stand by, we compile the Q&A, Russ. Our first question comes from Stephen Wiley with Steeples. You may perceive it with your question. Yeah, good morning.

The exposures of seem to be adequate to cause leukocyte mobilization, which is one of the key components for us to be able to have efficacy.

So we understand the potency of our molecule we've measured that in many settings and we also know that we're able to achieve those exposures to inhibit CXC of four to give us the efficacy that we're hoping to see.

Paula Ragan: Thanks for taking the questions. Paula, I was wondering if you could just kind of frame up expectations a little bit with respect to, I guess, what kind of data we might see in the abstract that gets released. And I guess how that may differ from what we could see at Iha. And it sounds like you said specifically that we'll be seeing data from the low and mid doses. Have you dose escalated patients up to that 600 million dose yet per the escalation protocol?

Yeah.

I guess kind of on.

On traditional metrics of like.

IC 50, 90, like what type of levels of rehab.

Yes, so the IC 50 from FX of course for non of molar and the I've seen items about 12 nanometer.

And so I guess the cross like I've certainly the fit me 400 milligrams per day gets us to the IC 50, and then the IC 90.

We're close to that with the 600, but of course, that's about maximum tolerated dose for the the window of the drug of non linear in terms of X X.

Exposure Mark.

Paula Ragan: Yeah, so I'll try to break that all down for you, Steve, and thank you so much for the question. So the way to think about Waldenstrom's, this is a disease, is obviously the heavy burden of IGM levels being excessively high, causing a lot of risk for some serious sequelae, like Hykepervis Kossi syndrome, and then that massive bone disease burden from the cancer itself causing hemoglobin impact

Okay.

A couple of things.

And then.

Maybe on when can you probably give an update on where you are more generally on patient identification efforts.

And kind of where registries are at these days.

Yes. So excellent question. So on patient identification. This is where we continue to partner with existing foundations that have their own registries as well as we.

We of our own internal patient advocacy group, that's been connecting with various sort of.

Subgroup that are formed within the wind community. So we continue to work with them partner with them work with existing registries and we certainly have been formulating our own registry to support the long term growth of maverick's afford to support these patients. So there's a bit of a stay tuned on sort of X four of specific registry plans, but.

Paula Ragan: For a patient, you want to see IGM dropping and hemoglobin rising as a function of being treated. So that's really the focus of our EHA data in terms of demonstrating changes in IGM levels and hemoglobin levels that could be indicative of the combination working better than brutinibalone. So we'll really be focusing on that. There are other phase 1B studies that, you know, sort of use this paradigm as well. So I think we're consistent with giving people the.

No that they are in the works and we're obviously wanting to appropriately dovetail into the community of that exist today and support them via our own efforts.

And then in terms of just one patient identification I think later this year, we will be focusing on some whim prevalence work, which will cross walk into some of the broader patient identification of initiatives that we have ongoing and I think there'll be sort of a good robust.

The review of some of those approaches towards the second half of this year.

Okay great.

Paula Ragan: the data set that can indicate our dual combination activity. When we think about the end of the year with Ash, it's really about response rates, and those take time to mature. Actually, typically, it takes about six months on treatment before our patients are going for CT scans and bone marrow assessments to really complete the definition of response rate that's required in these patient populations. So that's why we just need a longer time on study to be able to. to support a robust number of assessments across all our patients. And then, finally, you did mention the 600.

Very helpful. Thanks. Thank.

Thank you Mark.

Yes.

Thank you. Our next question comes from RJ <unk> with HC Wainwright you May proceed with your question.

Thank you good morning, Paul.

Quick question on my words before.

Alright.

Most of my questions on on the the current expectations on behalf of.

I got them, but.

Beyond.

What's going on right now on the phase one of these studies.

No.

Do you have.

Yeah.

Jim will outline as to how you would be going forward with this.

And to the phase two study.

And also.

The kind of give us the rough timeline as to when that could happen.

Yeah.

Yeah. So thanks, RK I think I'll start and then I'll invite you to add anything, but I think really for the clinical drug development, what we wanted to determine of the the activity and the potential benefit of the Dragon. The stay of one day of all dose.

Paula Ragan: I mean, the study is continuing to dose escalate. You know, it's an open-label study, and we haven't completed all the cohorts yet, so that's why we'll be focusing on the low-to-mid doses, but we'll certainly share as much data as we're able to. Okay, and I guess, Have you internally made the decision as to whether or not you're going to limit the enrollment up to 18. Or, do you think that you're going to get a sufficient amount of data? Verse 12.

Once we have a robust data set on hand, it's always that's the partner with the F D. A and other agency of the early in the process so that would be our intent.

And then I think once we both have the F D a and put in our data that will then be able to.

The project off of where the study will launch two and our view of it would be a straight into the study that would hopefully support registration, but we really need to generate the data set of course to have a mutually agreeable path forward both for the company and for our regulators of.

David would you like to add anything.

Thank you Paula.

Also yeah, we are actively working with leading investigators who who are really interest sitting in this population of the world Mealtime Walden shrunk to.

Look at the data and see the marriages and put together the best study designed to present the regulators. Obviously, we have a benchmark of how ibrutinib itself was approved on the debt is certainly one.

Area, we're carefully addressing on looking at it but also oh.

Or the potential of the scenario. So so we will be sharing more with you on all of the subsidy will continue thank you for the quest.

Thank you. The second question is on the core of <unk> trial.

The I understand you're going to give us a little bit of an update regarding enrollment in the midyear.

Paula Ragan: Well, the trial itself incorporates a maximum tolerated dose requirement. So the 12 to 18 builds in flexibility in the events that we have, dose-limiting toxicities. So that's where the flexibility comes in. Steve, it's not like we'll continue to try to escalate so long as the safety profile enables us to do so. The first two cohorts will reach through 600, so the last cohort C is a bit rounding out the total number of patients. So just stay tuned on that.

Or.

Comfortably this population and your experience so far the trial.

Again.

Similar question as is true.

When we could see the completion of the study or would be get that update also during the midyear.

Element update us do you know how.

How we should think about.

Youre not only of completing the study but are your conversations.

With the liberally regulators.

Yeah. So maybe just as a reminder on me.

We have shared that of the existing study design, which is randomized placebo controlled and double blinded.

Ken it's at a 12 month dosing period.

We have been heavily vetted by the FDA and EMA in terms of support for the design and statistical power, we feel extremely confident with the current study design and that that would be.

Paula Ragan: Understood. And then, just lastly, I'm just curious as to where things stand on severe.

Paula Ragan: Where things stand on severe Yeah, no, thank you. So the FDN trial is open and enrolling. In the context of COVID, especially last year and early this year, it was the most challenging study to enroll, given the short dosing time frame. These patients are immunocompromised.

Certainly enable an NDA and EMA filing from this one datasets from that continues to hold so I think the excitement for us of that when we provide guidance on enrollments that can readily sort of trigger of people can do the math on project off of one of the Pap topline data.

So that certainly as it continues to be consistent with our 2022 top line data guidance and we'll certainly look forward to being more specific in mid 2021.

Paula Ragan: The study is two weeks long, so we have always tried to prioritize patient safety and their need to come into hospitals for assessments. We do expect to have some initial data by the end of this year, but just in terms of patient numbers, what we've guided to is a smaller number of patients than, obviously, the total trial design. So we'll look forward to sharing what we're able to towards the end of the year. Thanks for taking the question. Thank you so much.

Thank you thank you Paula.

Thank you.

Thank you. Our next question comes from Miami from Tony with B. Riley You May proceed with your question.

Hi, Good morning theme with the thought of it was asked me on for Mike. Thanks for taking my questions and congratulations on all the progress on them.

Maybe the brief one on the whim patient enrollment and how that.

The sort of tracking it has been influenced by your efforts on patient identification.

And then also on that same train of thought how the patient identification efforts have had synergies on the SPM side and how you might think that influencing later stage trials as well.

Yeah. Thank you very much of the great question. So the.

The.

I'd I'd almost like the have you considered sort of three parallel I'm sort of of streams of work that you have lot of leverage with each other but certainly when we started the <unk> trial, which from design and planning was was certainly are a set of the timeframe at least you know two years ago at this point really in rare disease Youre working with.

Paula Ragan: Your next question comes from Mark Brom with Cowan. You may proceed with your question. Hi, thanks for taking my questions and congratulations on all the progress across the multiple programs. Paul, can you just remind us the different doses in the Walden's trial, just the kind of relative levels of CXR4 inhibition that you're expecting based on all the prior work you've done with the molecule? Sure, actually, I would invite Art Tavares to share that with you.

Centres of excellence Kols with known patients.

Instead of have that long chronic unmet need in our of sort of pent up demand for four of innovative study. So that's really been the the history around us on how we have enrolled and opened up the site work with investigators enrolled the trial of course in parallel what kind of we're playing the long game when is the rare genetic disease.

Under educated and Underdiagnosed and abroad clinical community of the bulk patient community. So along our journey as we built our own education and awareness efforts through a great MSL team and great patient advocacy team, you've actually naturally along the way come on Earth, new or newly found our newly identified when patients that have been.

Unknown Attendee: He's certainly one of our resident experts in exposure and inefficiency. So Art, Yes, hi, and thank you for the question. So the exposures that we're going after are very consistent with what we've seen from our WIME phase two trial. So the doses there, of course, are 200, 400, and then ultimately 600. And the exposures seem to be adequate to cause leukocyte mobilization, which is one of the key components for us to be able to have efficacy.

Appropriately directed to clinicians to learn about our trial and also continue to kind of broaden out the the overall.

Kind of activity between patients across the community. So I think it's the very natural synergy, but the patient identification efforts are really the long game and to build the the potential addressable patient populations.

F N went mavericks fourth of true.

And then the third question of the SDN are sort of dovetail and actually that's been a great opportunity for US one of the positive outputs of the N V. K efforts of the ban the.

Unknown Attendee: And so we understand the potency of our molecule. We've measured that in many settings, and we also know that we can. to achieve those exposures to inhibit CX-Z-4 to give us the efficacy that we're hoping to see. I guess, you know, kind of on traditional metrics of like, you know, IC 50, IC90, like, what type of levels are we at? Yes, so the IC 50 for Mavrexifor is 4 nanomolar, and the IC 90 is about 12 nanomolar.

The the panel that we're using for free of genetic testing for patients and for sorry for clinicians who have patients with immune deficiencies spans all of our large number of congenital neutropenia as of which SDN or some.

So some of that has been nicely leveraged with our ongoing studies and we've also through our patient advocacy efforts. There's a lot of overlap with some of the patient Foundation communities and we've had a nice synergy.

In terms of education and awareness to our SDN trial as well.

That address your question.

Yeah, absolutely that's really helpful. And then just maybe one more quick one on when did.

Unknown Attendee: And so, Art, just to cross-look, certainly the 50-400 milligrams per day gets us to the IC 50 and then the IC90. We're close to that with the 600, but, of course, it's about the maximum tolerated dose. So that's where the window is. The drug is nonlinear in terms of its exposure mark. Okay, that tells all things.

Could you provide kind of to the extent you're able to disclose the bit more color on what we might learn from incremental.

Sort of data from this phase two open label extension that you plan to share at the end of the year, whether it be from a safety or sort of the durability of response angle.

Yeah, I mean, the you know, it's I think you summarized it well with safety and durability, but obviously the the intense with with supporting when patients says is on lifelong treatment with Maverick before that's our expectation based on the data we know today so any <unk>.

Unknown Attendee: Maybe on WIM, can you, Paul, give an update on where you are more generally on patient identification efforts, kind of where registries are at these days? Yeah, so excellent question.

Data that we generate them under close you.

Watch around safety and durability continues to support the the totality of data that would enable.

The strength of patients to be comfortable with the data of course of obviously the regulators as well. So I think it's I'm just sort of stay tuned and the way.

Paula Ragan: So on patient identification, this is where we continue to partner with existing foundations that have their own registries, as well as we have our own internal patient advocacy group that's been connecting with various subgroups that have formed within the WIM community. So we continue to work with them, partner with them, work with existing registries, and we certainly have been formulating our own registry to support the long-term growth of Mavericks before to support these patients.

We look forward to sharing that as of the emerges.

Great really appreciate the time, thanks for taking my questions.

Yes.

Thank you. Our next question comes from Arlinda Lee with Canaccord you May proceed with your question.

Hi, guys. Thanks for taking my question.

You guys alluded to marine distillate any toxicity.

Could you talk a little bit about what you would expect this might be and then can you comment on whether you expect dosing to be the same across.

Of the various disease indication. Thank you.

Sure. Thanks, Dan.

I'd like to take that.

Yes sure yeah. So they were.

In terms of them on board, except for the data we have in when it is used as monotherapy. It really has been very well tolerated.

So we don't really have any expected dose limiting toxicities of directly from my worry except for the alone.

Paula Ragan: So there's a bit of a state-tuned on sort of X-For's specific registry plans, but know that they're in the works, and we're obviously wanting to appropriately dovetail into the communities that exist today and support them via our own efforts. And then in terms of just when patient identification, I think later this year we will be focusing on some WIM prevalence work, which will crosswalk into some of the broader patient identification initiatives that we have ongoing. And I think there'll be sort of a good, robust overview of some of those approaches in the second half of this year.

However, when you use it in combination with Ibrutinib I'm sure you know there is a.

Favorite of safety issues with chronic treatment with Ibrutinib.

The already to me at least in the label and when you're dosing combination we have to monitor those very carefully on Steve I think my worry except for the is having any.

The effects, so thats, mostly what we are tracking.

Regarding.

The weather, we expect the same of different dose.

Hands on the data we have.

Confident for the whim syndrome, we have the right dose that's the 400 milligrams per day.

Well the strong we are dose escalating up to 600 on based on the total without really T. S. Weightless day, because he segment of the week.

We chose the dose of that gave you the best day.

[noise] benefit risk profile.

Paula Ragan: Okay, great. That's very helpful. Thanks. Thank you, Mark. Thank you. Our next question comes from R.K. Ramcon with H.C. Wainwright. You may proceed with your question.

I hope that answer your question.

Thank you.

Yeah.

Thank you. Our next question comes from Jay Good job with Roth Capital Partners. You May proceed with your question.

Okay.

Yeah.

Yeah.

Is that group your line is on mute please on mute.

Yeah.

Yeah.

And im not showing any further questions at this time I would now like to turn the call back over to Paul The Reagan for any further remarks.

Paula Ragan: Thank you. Good morning, Paula. A quick question on Mallorix for most of my questions on the current expectations. I have them. Beyond what's going on right now in the phase 1B study, you know. Do you have, um, you know, a general outline of how you would be going forward with this into the phase two study and also, could you kind of give us a rough timeline as to when that could happen?

Well, we'd like to say, thank you very much for joining the call today and if you have any further questions. Please don't hesitate to reach out and we hope you enjoy the rest of your day. Thank you so much again.

Thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.

Paula Ragan: Yeah, so thanks, RK. I think I'll start and then I'll invite you to add anything. But I think really for clinical drug development, what we want to determine in phase 1B is the activity and potential benefit of the drug in phase 1B as well as the dose. Once we have a robust data set in hand, it's always best to partner with the FDA and other agencies early in the process. So that would be our intent.

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Yes.

Yeah.

Yes.

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Paula Ragan: And then I think once we both have the FDA's input and our data set, we'll then be able to project off of where this study will launch. In our view, it would be straight into a study that would hopefully support registration, but we really need to generate the data set, of course, to have a mutually agreeable pass forward both for the company and for regulators. Diego, would you like to add anything?

Diego: Yeah, thank you, Paula. Also, yeah, we're actively working with leading investigators who are really interested in this population of Double Mutant Waldenstrom to look at the data as it emerges and put together a study designed to present to regulators. Obviously, we have benchmarks of how Ibrutinif itself was approved, and that is certainly one area we're carefully addressing and looking at, but also other potential scenarios. So we will be sharing more with you and others as the work continues. Thank you for the question.

Paula Ragan: Thank you. The second question is on the poor WIM trial. We understand, you know, you're going to give us a little bit of an update regarding enrollment in the mid-year. However, considering this population and your experience so far with the trial, again, a similar question as to when we could see the completion of this study, or would we get that update also during the meteor enrollment update as to, you know, how we should think about your complete, not only your completion of the study, but your conversations with the regulator

Paula Ragan: Yeah, so maybe just as a reminder, we have shared that the existing study design, which is randomized, placebo-controlled, and double-blinded, and it's a 12-month dosing period, has been heavily vetted by the FDA and EMA in terms of support for the design and statistical power. So you feel extremely confident with the current study design and that that would certainly enable an NDA and EMA filing from this one data set. And that continues to hold.

Paula Ragan: So I think the excitement for us is that when we provide guidance on enrollment, that can readily sort of trigger people to do the math and project off of when we'll have top-line data. So that certainly continues to be consistent with our 2022 top-line data guidance, and I will certainly look forward to being more specific in mid-2020.

Paula Ragan: Thank you. Thank you, Paula.

Operator: Thank you. Our next question. Close from Wyonkhamstowne with B. Riley. Can you be able to achieve with your question? Hi, good morning, Seymn. This is Sahel Kazmian on my own.

Paula Ragan: Thanks for taking our questions, and congratulations on all the progress. Maybe a brief one on the WIMM patient enrollment and how that's sort of tracking and has been influenced by your efforts in patient identification. And then also on that same train of thought, how the patient identification efforts have had synergies on the SDM side and, you know, how you might think that might influence later stage trials as well. Yeah, thank you very much for the great question. So the answer is...

Paula Ragan: I'd almost like to consider sort of three parallel streams of work that do have leverage with each other. But certainly, when we started the four-oim trial, which from design and planning was certainly set at a time frame at least two years ago at this point, really, in rare disease, you're working with Centers of Excellence, K-A-WLs with known patients. Decent said we have had that long, chronic unmet need in our sort of pent-up demand for innovative study.

Paula Ragan: So that's really been the history around us and how we have enrolled, opened up sites, worked with investigators, and enrolled the trial. Of course, in parallel, we're playing the long game. WIM is a rare genetic disease undereducated and underdiagnosed in the broad... clinical communities as well as patient communities.

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Paula Ragan: So along our journey, as we built our own education and awareness efforts through a great MSL team and a great patient advocacy team, we've actually naturally, along the way, unearthed new or newly found or newly identified patients that have been appropriately directed to clinicians to learn about our trial and also continue to kind of broaden out the overall, um, connectivity between patients across the community. So I think it's a very natural synergy, but the patient identification efforts are really the long game to build potential addressable patient populations if and when Mavericks scores is approved.

Paula Ragan: And then the third question is the SCN sort of dovetail, and actually that's been a great opportunity for us. One of the positive outputs of the NVK efforts has been the panel that we're using for free genetic testing for patients and sorry for clinicians with patients with immune deficiencies, which spans all a large number of congenital neutropenias, of which fdineas are some. So some of that has been nicely leveraged with our ongoing studies.

Paula Ragan: And we've also, through our patient advocacy efforts, there's a lot of overlap with some of the patient foundation communities, and we've had a nice synergy in terms of education and awareness about our S-D-N trial as well. So I hope that addressed your question. Yeah, absolutely. That's really helpful. And then maybe one more quick one on WIM is, could you please provide kind of to the extent you're able to disclose a bit more color on what we might learn from incremental sort of data from the space to open label extension that you plan to share at the end of the year, whether it be from a safety or sort of durability of response angle?

Paula Ragan: Yeah, I mean, you know, I think you summarized it with safety and durability, but obviously, the intent with supporting WIMP patients is lifelong treatment with Maverick before. That's our expectation based on the data we know today. So any data that we generate under close, you know, watch around safety and durability continues to support the totality of data that would enable physicians and patients to be all comfortable with the data. Of course, obviously, the regulators as well.

Paula Ragan: So I think it's, you know, just a bit of stay tuned, and we look forward to sharing that as an emergency. Great. I really appreciate the time.

Paula Ragan: Thanks for taking our question. Thank you. Thank you. Your next question. Also, Marlinda Lee with Cantercourt.

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Operator: You may proceed with your question. Hi guys, thanks for taking my questions. You guys alluded to nearing dosaline toxicity. Could you talk a little bit about what you would expect those might be? And then can you comment on whether you expect dosing to be the same across the various disease indications?

Paula Ragan: Sure, thanks. Diego, would you like to take this? Yes, sure.

Diego: Yes, sure. Yeah, so in terms of Mavorica, for the data we have in, when it is used as monotherapy, it really has been very well tolerated. So we don't really have any expected limiting toxicity directly from Mavorexia alone. However, when you use it in combination with ibupinib, I'm sure you know there are several safety issues with chronic treatment with ibuputinin. They're all very clearly listed on the label, and when you take those in combination, we have to monitor those very carefully and see if adding Maboric Saffori is having any effects.

Diego: So that's mostly what we are tracking, regarding whether we expect the same results at different doses; that will depend on the data. We're confident about WIMS syndrome. We have the right dose, that's 400 milligrams per day. Waldenstrom, we are dose escalating up to 600. And based on the tolerability, as well as the efficacy signal, we will choose the dose that gives the best benefit risk profile. I hope that answers your question. Thank you.

Operator: Thank you. Our next question comes from Jake Vigilal, with Roth Capital Partners, you may perceive the question. Is that great if your line is on mute, please on mute. And I'm not throwing any further questions at this time. I would not like to turn the call back over to Paula Rakein for any further questions.

Paula Ragan: We'd like to say thank you very much for joining us today. And if you have any further questions, please don't have to reach out, and we hope you enjoy the rest of your day. Thank you so much again. Thank you, ladies and gentlemen. This concludes today's conference call. Thank you for participating. You may not disconnect.

Operator: The President, I don't know, and so much, and I'm going to be able to be. I don't know.

Operator: And so on the end up. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. The President, Thank you.

Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.