Q4 2019 Earnings Call
Greetings and welcome to export Pharmaceuticals fourth quarter and for your 2019 business highlights <unk> results conference call.
Operator: Greetings and welcome to X4 Pharmaceuticals' fourth quarter and full year 2019 Business Highlights and Financial 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 call is being recorded. It is now my pleasure to introduce your host, Candice Ellis, Director of Corporate Communications and Investor Relations at X4. You may begin. Thank you,
At this time all participants are in listen only mode. A question and answer session with all the formal presentation. As a reminder, this conference call is being recorded just not my first introduce your host Kinda Snowless director of corporate Communications and Investor Relations. It acts for you may begin.
Thank you Kevin and good morning, everyone. Thanks, so much for joining us as we provide a recap of our key activities during 2019 and discuss our strategy and upcoming milestones for 2020.
Candice Ellis: Thanks so much for joining us as we provide a recap of our key activities during 2019 and discuss our strategy and upcoming milestones.
Candice Ellis: Milestones for 2020. Presenting on today's call will be our Chief Executive Officer, Dr. Paula Ragan, our Chief Medical Officer, Dr. Lynn Kelly, and our Chief Financial Officer, Adam Mostafa. Following prepared remarks by each, we will open the call to your questions.
Presenting on today's call will be our Chief Executive Officer, Dr. Paulo, Reagan, our Chief Medical Officer, Dr., Lin Kelly, and our Chief Financial Officer, Adam the stuff.
During prepared remarks by age we'll open the call to your question.
Operator: to your questions. As a reminder on today's
As a reminder, on today's call will be making forward looking statements regarding our regulatory and product development plans as well as our research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted a description of these risks can be found in our most recent form 10-K on file with the FCC.
Candice Ellis: In today's call, we will be making forward-looking statements regarding our regulatory and product development plans, as well as our research activities. These statements are subject to risks and uncertainties that may cause...
Operator: Thank you.
Paula Ragan: I'd now like to turn the call over to our Chief Executive Officer, Dr. Paula Ragan.
Now I'd like to turn the call over to our Chief Executive Officer, Dr., Paul There Reagan.
Paula Ragan: Thanks, Candice, and thank you, everyone, for joining us on this call this morning. 2019 was a remarkable year for X4, with significant achievements made across our entire organization, and specifically, achievements that have allowed us to further strengthen our leadership position in the discovery and development of therapies to treat rare diseases resulting from the dysfunction of the CXCR4 pathway. 2019 saw the debut of X4 as a public company, and we were able to successfully raise more than $150 million during the year to further support our mission.
Thanks, Candice and thank you everyone for joining us on this call. This morning.
2019, with a remarkable year correct for with significant achievements made across our entire organization.
Specifically achievements that have allowed us to further strengthen our leadership position in the discovery and development of therapies to treat rare diseases, resulting from the just function of the CX here for pathway.
2019 saw the debut of X for the public company and we were able to successfully raised more than $150 million during the year to further support our mission.
Paula Ragan: I'd like to take this opportunity to thank our shareholders for their continued support of the company, as well as our analysts who have played an important role in sharing our story. I'm going to focus on our 2019 achievements today, not only to highlight our LEAD programs but also to provide a framework to discuss our strategy going forward, as well as key upcoming milestones, as Candice has mentioned. Importantly, in June of last year, we initiated the pivotal Phase 3 clinical trial of our lead therapeutic candidate, Mavarixifor, for the treatment of Wimp Syndrome. As a reminder, Mavarixifor is a first-in-class oral small molecule antagonist of the chemokine receptor CXCR4, a receptor known to play a key role in enabling the healthy trafficking of immune cells and effective immunosurveillance. We are actively dosing patients in the Phase 3 trial, and enrollment is on track to be completed in the second half of 2020. Lynn will discuss the trial in more detail in a moment.
Like to take this opportunity to thank our shareholders for their continued support of the company as well as our analyst who played an important role and sharing our story.
I'm going to focus on our 2019 achievements today not only to highlight our lead programs, but to also provide a framework to discuss our strategy going forward as well as key upcoming milestones as Kansas has mentioned.
Importantly in June of last year, we initiated the pivotal phase three clinical trial, our lead therapeutic candidate Mavericks before.
For the treatment of one syndrome.
As a reminder, mavericks before as a first in class oral small molecule antagonist of the chemo kind of receptor CX here for a receptor known to play a key role and enabling the healthy trafficking of immune cells and effective and you know surveillance.
We are actively dosing patients in the phase three trial and enrollment is on track to be completed in the second half of 2020.
And we'll discuss the trial in more details in a moment.
Paula Ragan: But we remain on track to report top-line data from our global study in the second half of 2021. Furthermore, during 2019, Maverick Sephora was granted breakthrough therapy designation by the FDA for the treatment of WIM, which we believe not only highlights the severity of the disease but also the strength of our Phase II data. As you may know, breakthrough therapy designation is granted to facilitate the development and regulatory review of an investigational new drug. There are two key components required to support breakthrough designation, the first being that the drug is intended to treat a serious or life-threatening condition where there is an unmet need, and the second is preliminary clinical evidence that demonstrates the drug may provide substantial improvements over any available therapy.
So we remain on track to report topline data from our global study in the second half of 2021.
During 2019 Mavericks before it was granted breakthrough therapy designation by the FDA for the treatment of win which we believe not only highlights the severity of the disease, but also the strength of our phase two data.
As you May know breakthrough therapy designation is granted to facilitate the development and regulatory review about an investigational new drug.
There are two key components required to support breakthrough designation the first being that the drug is intended to treat a serious or life threatening condition, where there's an unmet need and the second is preliminary clinical evidence that demonstrates the drug may provide substantial improvements over any available therapy.
Paula Ragan: We are very pleased that the FDA recognized Maverix IV's potential to treat Wim's syndrome as a serious or life-threatening disease with its grant of breakthrough therapy designation. We also received orphan drug designation from the European Commission for Mavarixifor and WIM in 2019, having already received orphan designation in the U.S. the prior year. During the year, we also completed scientific advice with the EMA, aligning the WIM Phase 3 registration trial globally. On April 7th, we will be holding an Analyst Day, which will also be webcast, to provide a deeper look into Wim Syndrome. We will discuss the Wim patient experience and severity of the disease, have an opportunity to hear directly from a leading KOL who treats Wim patients, and provide an update on the prevalence of the disease.
We're very pleased that the after you recognized Maverick force potential to treat whims syndrome, as a serious or life threatening disease with its grant a breakthrough therapy designation.
We also received orphan drug designation from the European Commission for Mavericks before in when in 2019, having already received orphan designation in the U.S. the prior year.
During the year. We also completed scientific advice would be a may aligning the women phase three registration trial globally.
On April 7th we will be holding an analyst day, which will also be webcast to provide a deeper look into women syndrome.
I'll discuss the when patient experience and severity of the disease have an opportunity to hear directly from a leading kaombo, who treat when patients and provide an update on the prevalence of the disease.
Paula Ragan: Then, mid-year, we plan to announce additional data from the Open Label Extension portion of our WHAM Phase 2 study, including updates to clinical infection rates and warp burden. In addition, in 2019, we initiated two Phase 1B studies examining the safety and tolerability of Maverix X4, in addition to certain efficacy measures. One in the treatment of severe congenital neutropenia, or SCN, and the other in Waldenstrom's macroglobulinemia. We anticipate initial clinical data from both of these proof-of-concept trials in the second half of 2020. Lim will provide additional detail regarding both of these trials in just a moment.
Then midyear, we plan to announce additional data from the open label extension portion of our when phase two study, including updates to clinical infection rates in weren't burden.
In addition in 2019, we initiated two phase one be studies examining the safety and Tolerability of Mavericks before in addition to certain efficacy measures.
One in the treatment of severe congenital neutropenia or SCM and the other and Waldenstrms Macroglobulinemia. We anticipate initial clinical data from both of these proof of concept trials in the second half or 2020.
Limb will provide additional detail regarding both of these trials in just a moment.
Paula Ragan: Related to our efforts to treat Waldenstrom's, in May last year, Maverick Sephora was selected for investment by the Leukemia and Lymphoma Society's Therapy Acceleration Program, or TAP. CAP is a strategic initiative of the LLS that creates alliances to speed the development of carefully chosen new therapies for blood cancers. This collaboration focuses on accelerating the development of Mavirexifor for the treatment of patients with this rare form of non-Hodgkin's lymphoma. In 2019, we also entered into a solid tumor oncology development and commercialization agreement with Abisko Therapeutics in Greater China to develop and commercialize Maverix X4 in combination with checkpoint inhibitors or other agents in solid tumor oncology settings in that region. And just last month, we were granted a new composition of matter patent on Mavrixifora that we expect will provide us with exclusivity on the compound through 2038, further enhancing our patent portfolio and extending our potential commercial horizon.
Related to our efforts to treat Wong from in May last year Mavericks before it was selected for investments by the leukemia and lymphoma Society therapy acceleration program or tap.
As a strategic initiative of the LLS that creates alliances to be the development carefully chosen new therapies for blood cancers.
This collaboration focuses on accelerating the development of Mavericks before for the treatment of patients with this rare form of non Hodgkin's lymphoma.
In 2019, we also entered into a solid tumor oncology development and commercialization agreement with a best go therapeutics in greater China to develop and commercialize Mavericks before in combination with checkpoint inhibitors or other agents in solid tumor oncology settings in that region.
And just last month, we were granted a new composition of matter pens on Mavericks before that we expect will provide us exclusivity on the compound through 2038.
Further enhancing our patent portfolio and extending our potential commercial horizon.
Lynn Kelly: On the governance and leadership front, we were able to significantly strengthen our board of directors, adding Dr. Rene Russo, Mr. David McGurr, Dr. Murray Stewart, and Mr. William Olitsky to the board, all of whom have significant leadership experience and impressive records of success at public life science companies. We also filled several key positions in-house, including our Chief Medical Officer, Dr. Lynn Kelly, who is guiding and overseeing our clinical programs, our General Counsel, Derek Meisner, who brings broad experience at public companies as well as the FCC, and our Senior Vice President of Research and Development, Dr. Renato Skrl, who is an expert in CXCR4 biology, working to strategically expand our research efforts while also managing a research facility in Additionally, we recently enhanced our patient advocacy efforts with the hiring of Michele Ray, our Vice President of Patient Affairs and Patient Advocacy, who brings critical expertise and understanding to the rare disease business. I'm now going to turn the call over to our Chief Medical Officer, Dr. Lynn Kelley, to discuss our clinical trial progress.
On the governance and leadership front, we were able to significantly strengthen our board of directors, adding dr. Rene Rousso Mr., David Macgregor, Dr., Mary Stewart, and Mr., William Alisky to the board all of whom have significant leadership experience and impressive records of success at public life Science companies.
We also sold several key positions in house, including our Chief Medical Officer, Dr. Lin Kelly, who is guiding in overseeing our clinical programs. Our general counsel Derrick Meissner, who brings broad experience at public companies as well as the FCC and our senior Vice President of research and development Dr. analysis.
Girl, who is an expert and seek CR for biology working to strategically expand our research efforts, while also managing a research facility in Vienna, Austria.
Additionally, we recently enhanced our patient advocacy efforts, but the hiring of Michel Ray our vice President of patient affairs and patient advocacy the brings critical expertise and understanding in the rare disease business.
I'm now going to turn the call over to our Chief Medical Officer, Dr. Lin Kelly to discuss our clinical trial progress then.
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Thanks, Paul and good morning, everyone. As Paul mentioned, we were able to make significant progress in the advancement of our clinical efforts during 2019.
Lynn Kelly: Thanks Paula, and good morning everyone. As Paula mentioned, we were able to make significant progress in the advancement of our clinical efforts during 2019. In the middle of 2019, we initiated the pivotal Phase III clinical trial of our lead therapeutic candidate, Abarixifor, for the treatment of Wim's syndrome, which is a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. Our Phase III trial, which we've branded 4-WIM, is a global, 52-week, randomized, double-blind, placebo- We expect to enroll 18 to 28 subjects in approximately 20 countries, followed by an open-label extension trial. We expect to complete full enrollment in the second half of this year, and we continue to expect top-line results from the 4WM trial in the second half of 2021.
In the middle of 2019, we initiated the pivotal phase three clinical trials of our lead therapeutic candidate ever except for for the treatment of when syndrome, which is a rare inherited primary immunodeficiency disease caused by genetic mutations in the CX here for receptor gene.
Our phase three trial, which we branded for whim is a global 52 week randomized double blind placebo controlled multicenter study designed to evaluate the safety and efficacy of Mavericks before in genetically confirmed when patients.
We expect to enroll 18 to 28 subjects in approximately 20 countries followed by an open label extension trial.
We expect to complete full enrollment in the second half of this year and we continue to expect topline results from the four when trial in the second half of Twentytwenty one.
As Paul mentioned earlier, we recently initiated two additional clinical trials, both crucis concept phase one be trials of Mavericks before one in patients with severe congenital neutropenia, which is a group of rare blood disorders characterized by abnormally low levels of white blood cells.
Lynn Kelly: As Paula mentioned earlier, we recently initiated two additional clinical trials, both crucif concept, phase 1b trials of Mavarixifor, one in patients with severe congenital neutropenia, which is a group of rare blood disorders characterized by abnormally low levels of white blood cells, and the other in combination with the BTK inhibitor abrutinib in patients with Waldenstrom's macroglobulinemia, which is a rare form First, I'd like to provide some additional context for our efforts in SCN.
And the other in combination with the BTK inhibitor ibrutinib in patients with Waldenstrms, Macroglobulinemia, which is a rare form of non Hodgkin's lymphoma.
First I'd like to provide some additional context to our efforts in S. C N.
Lynn Kelly: This disease often presents as a diagnostic challenge for physicians, and there is an unmet clinical need for targeted treatment options that may be better tolerated than existing therapies. Current treatments are limited to nonspecific stimulation of the bone marrow with daily injections of Granulocyte Colony Stimulating Factor, or GCSF, and antibiotics given prophylactically or to treat infections. Unfortunately, GCSF carries with it a high incidence of adverse events. It can cause bone pain, as well as injection site reactions, and in rare instances, high chronic doses of GCSF have been associated with myelodysplasia and acute myeloid leukemia in this patient population.
This disease, often it presents as a diagnostic challenge for physicians and there's an unmet clinical need for targeted treatment options that may be better tolerated than existing therapies.
Current treatments are limited to non specific stimulation up the bone marrow with daily injections of Greenfield site colony stimulating factor or G CSF and with the antibiotics, given prophylactically or to treat infections. Unfortunately, GE Si es half carries with it a high incidence of adverse.
Yes, it can cause bone pain, as well as injection site reactions and in rare instances hi, chronic doses of G. CSF had been associated Milo dysplasia and acute myeloid leukemia in this patient population.
Lynn Kelly: The recently initiated Phase 1b trial is a 14-day trial designed to assess the safety and tolerability of daily oral Mavarixifor in patients with SCN and other selected congenital neutropenia disorders. In addition, the trial will evaluate the neutrophil response in this patient population as an independent agent or in combination with GCSF, comparing neutrophil counts at baseline and at completion. The trial is designed to enroll up to 45 patients in total. Given our depth of experience with Mavirixifor, our goal here is to achieve proof of concept to support interactions with the FDA regarding a proposed registrational trial. We anticipate initial clinical data from our SCM trial in the second half of 2020. Now, turning to Waldenstrom's macroglobulinemia, a rare form of non-Hodgkin's lymphoma.
The recently initiated phase one be trial is a 14 day trial designed to assess safety and Tolerability of daily oral never except for in patients with S.C.N. and other selected congenital neutropenia disorders.
In addition, the trial will evaluate Nutra Flo response in this patient population as an independent agent or in combination with G. CSF comparing neutrophil counts at baseline had completion.
The trial is designed to enroll up to 45 patients in total given our depth of experience with Mavericks before our goal here is to achieve proof of concept to support interactions with the FDA regarding a proposed registrational trial.
We anticipate initial clinical data from our SCM trial in the second half of Twentytwenty.
Now turning to Waldenstrms macroglobulinemia, a rare form of non Hodgkin's lymphoma.
Lynn Kelly: In December, we initiated a Phase 1b clinical trial of Mavirixifor in combination with Abrutinib in patients with Waldenstrom's macroglobulinemia. The trial will focus on and enroll patients who have acquired a gain-of-function mutation in the CXCR4 receptor in addition to the MI-D88 mutation. These patients have been shown to have a shallower response and to take longer to respond relative to the single mutant patient. The Phase 1b multicenter open-label dose escalation trial is designed to determine the appropriate dose and to assess the safety and tolerability of Mavrexifor in combination with abrutinib. In addition, the trial is designed to measure changes in serum immunoglobulin M, or IgM, and hemoglobin from baseline. Both of these biomarkers are key elements in the clinical response in Waldenstrom's patients.
In December we initiated a phase one be clinical trial of Mavericks before in combination with Ibrutinib inpatient football insurance backer Gloppy anemia.
The trial will focus on and enroll patients who have acquired a gain a function mutation in the CX here for receptor. In addition to the Mydeighty eight mutation.
Hallmark of Waldenstrms diagnosis. These patients have is shown to have a shallower response and to take longer to respond relative to the single mutant patients.
The phase one be multicenter open label dose escalation trial is designed to determine the appropriate dose and to assess the safety and tolerability of Mavericks before in combination with Ibrutinib.
In addition, the trials designed to measure changes in serum analytical lobbying and where I G M.
Hemoglobin from baseline both of these biomarkers are key elements in the clinical response in Waldenstrms patients.
Lynn Kelly: The clinical trial is expected to enroll approximately 12 to 18 patients. As Paula mentioned, this trial is being conducted as part of a collaboration with the Leukemia and Lymphoma Society. We anticipate initial clinical trial data from a Waldenstrom's trial in the second half of 2020. I'm now going to turn the call over to our Chief Financial Officer, Adam Mostafa, to discuss our financial results. Adam?
The clinical trials expected to enroll approximately 12 to 18 patients as Paul mentioned this trial is being conducted as part of the collaboration with the leukemia and lymphoma Society.
I anticipate initial clinical trial data from a waldenstrms trial in the second half of Twentytwenty.
I'm now going to turn the call over to our Chief Financial Officer, Adam Mustapha to discuss our financial results Adam Thanks, Lynn and thanks to all in the call today.
Adam S. Mostafa: Thanks, Lynn, and thanks to you all on the call today. As we embark upon what we believe will be a very productive 2020, we enter the year in a strong financial position. As Paul mentioned, this was possible due to the completion of two successful public stock offerings that raised approximately $150 million and added a blue chip group of knowledgeable and supportive institutional investors. Overall, these financings put us in a strong cash position that is expected to fund our current operating plan into early 2022. That runway excludes any potential cash benefit from warrant exercise proceeds or any additional borrowings under our debt facility.
As we embark upon what we believe will be a very productive 2020, we entered the year in a strong financial position.
As Paul mentioned the possible due to the completion of two successful public stock offerings that raised approximately $150 million and added a blue chip group of knowledgeable and supportive institutional investors.
Overall these financings put us in a strong cash position that is expected to fund our current operating plan into early 2022.
That runway excludes any potential cash benefit from warrant exercise proceeds or any additional borrowings under our debt facility.
Adam S. Mostafa: As for the details of the fourth quarter and full year of 2019, we ended 2019 with $128.1 million in cash, cash equivalents, and restricted cash. This is compared to $77 million as of September 30, 2019, with the increase driven predominantly by our successful $65 million November public offering. Our research and development expenses were $7.1 million for the fourth quarter of 2019 and $30.2 million for the year ended December 31, 2019, as compared to $4.7 million and $20.3 million for the comparable periods in 2018, respectively. Our general and administrative expenses were $3.9 million for the fourth quarter of 2019 and $17.6 million for the year ended December 31, 2019, as compared to $3.4 million and $8.7 million for the comparable periods in 2018, respectively.
As for the details on the fourth quarter and full year 2019.
We ended 2019 with $128.1 million in cash cash equivalents unrestricted cash this is compared to $77 million as of September Thirtyth 2019, with the increase driven predominantly by our successful 65 million dollar November public offering.
Our research and development expenses were $7.1 million for the fourth quarter of 2019 and $30.2 million for the year ended December 30, Onest 2019.
As compared to $4.7 million and $20.3 million for the comparable periods in 2018, respectively.
Our general and administrative expenses were $3.9 million for the fourth quarter of 2019 and $17.6 million for the year ended December 30, Onest 2019, as compared to $3.4 million and $8.7 million for the comparable periods for 2018, respectively.
And we reported a net loss of $10.8 million for the fourth quarter of 2019, and a net loss of $52.8 million for the year ended December 31st 2019, as compared to a net loss of $11.3 million and a net loss of $33.3 million for the comparable.
Adam S. Mostafa: And we reported a net loss of $10.8 million for the fourth quarter of 2019 and a net loss of $52.8 million for the year ended December 31st, 2019, as compared to a net loss of $11.3 million and a net loss of $33.3 million for the comparable periods in 2018, respectively. Note that the net loss of $52.8 million for the 2019 year includes $3.9 million of non-cash losses related to the sale of in-process research and development intangible assets. I'll now pass the call back to Paula for our concluding remarks before we open it up for your questions.
As an 18, respectively.
No that the net loss of $52.8 million for the 2019 year includes $3.9 million of noncash losses related to the shell in process research and development intangible assets.
I'll now pass the call back to Paula for concluding remarks before we open it up for your questions Paula.
Thanks, So much Adam as you can see 2019 was a pivotal year for us our first year as a public company. The launch of our phase three registration trials Mavericks before and when the initiation of two additional exciting clinical trials that will deliver initial results this year and the strengthening of our base.
Paula Ragan: Thanks so much, Adam. As you can see, 2019 was a pivotal year for us. Our first year as a public company, the launch of our phase three registration trial of Maverix X4 and WHIM, the initiation of two additional exciting clinical trials that will deliver initial results this year, and the strengthening of our balance sheet, our management team, and our board of directors. This is all in anticipation of a very busy next 12 to 18 months, during which time we will expect to complete enrollment in WIM, see proof of concept for Maver We look forward to updating you on our progress over the coming year and hope you will participate in our upcoming Analyst Day on April 7th for a deeper dive into our focus on Wim Syndrome. And with that, why don't we open it up to questions? Kevin?
Balance sheet, our management team and our board of directors.
This is all in anticipation of a very busy next 12 to 18 months during which time, we will expect to complete enrollment and when I see proof of concept a mavericks before in additional indications and expand upon our commercial preparation efforts in anticipation of our topline results from the four Wham phase three trial and the second half.
2021.
We look forward to updating you on our progress over the coming year and hope you will participate in our upcoming analyst day on April 7th for a deeper dive into our focus on when syndrome.
And with that why don't we open it up to questions Kevin.
Ladies and gentlemen, if you have a question or comment at this time. Please press the star than the one key when you touched on telephone. If your question has been answered your schumer yourself from acute these first the balance sheet.
Our first question come from stuff movie with Stifel.
Hey, good morning, guys. Thanks for taking my questions.
Operator: Ladies and gentlemen, if you have a question or a comment at this time, please press the star then the 1 key on your touchtone telephone. If your question has been answered and you wish to remove yourself from the queue, please press the pound key. Our first question comes from Stephen Willey. Yeah, good morning, guys.
Probably in a normal to answer this morning, but I'm just kind of curious you know you talked about.
The the.
The pivotal for wind trial and then this is obviously kind of global.
Undertaking and Theres, obviously, a lot of investor concern around from the.
Stephen Douglas Willey: Thanks for taking the questions. Probably an unknowable answer at this point, but just kind of curious, you know, you talked about the pivotal four-way trial, and this is obviously kind of a global, a global undertaking. And there's obviously a lot of investor concern around some of the development timelines with some of the ex-US and perhaps even US Hospitals becoming more restrictive with respect to visitations and kind of non-core activities. So just kind of wondering, you know, how closely you are monitoring your trial sites and how much cushion do you think is built into your timelines, both with respect to completion of enrollment and also just with respect to top-line data?
Element Taiwan's with some of the actually U.S. and.
Perhaps even U.S.
Hospitals, becoming more restricted with respect.
To visitations and the kind of non.
Core activity so.
Just kind of wondering.
Do you how closely kind of argue monitoring.
Your trial sites and how much cushion do you think is built into your.
Your timeline, coupled with respect to completion of enrollment and also just with respect to topline data.
Hi, Hi, Steve. Thanks for the question I think to Echo back your comment if it is unknowable at this point, but all we can say is near the when trial as global and have we've always tried to mitigate enrollments by having multiple countries open with multiple sites its 18th 20 patients.
Paula Ragan: Hi Steve. Thanks for the question. I think to echo your comment, it is unknowable at this point, but all we can say is, you know, the WIM trial is global, and we've always tried to mitigate enrollment by having multiple countries open with multiple sites. It's 18 to 28 patients, and at this point, we don't see a significant impact on that projection. However, things are changing rapidly, as you've stated. So, we continue to monitor. We continue to closely connect with our clinicians to make sure that they're still guided appropriately, and at this point, we've received no inbound communications that their operations are changing.
And at this point, we don't see significant impact to that projection. However, things are changing rapidly as we've stated. So we continue to monitor we continue to Scott closely connect with our clinicians to make sure that they're still guided appropriately and at this point we've received inbound.
Communications that their operations are changing.
Okay. That's helpful.
And then just want to think about.
The severe congenital neutropenia trial.
Relative to I guess the phase two when trial that was conducted I know that you.
Took your first 24 hour neutral evaluation I think in the phase two week, five and I know here you're doing it at week. Two so can you maybe just talk a little bit about the time to steady state and just whether or not you think you know.
Stephen Douglas Willey: Okay, that's helpful. And then just when I think about.., the Severe Congenital Neutropenia Trial. Relative to, I guess, the Phase 2 WIM trial that was conducted, I know that you took your first 24-hour neutrophil evaluation, I think, in the Phase 2 at Week 5, and I know here you're doing it at Week 2, so can you maybe just talk a little bit about the time to steady state and just whether or not you think, you know, two weeks of exposure in what is, I guess, a fundamentally different genetic disease is sufficient to have an impact on neutrophils?
Two weeks of exposure in what is I guess a fundamentally.
Different genetic disease.
Tom is sufficient to have an impact on neutrophils.
Yeah. This is land 'em, we do so the 14 day time period for the clinical study a one of the things. It is based upon is the knowledge that steady state was reached for the drug based upon the pharma code kinetics in about seven days and so it also is informed by our healthy human volunteer study previously that demonstrated.
Lynn Kelly: Yeah, this is Lynn. We do, so the 14-day time period for the clinical study, one of the things it is based upon is the knowledge that steady state was reached for the drug based upon pharmacokinetics in about seven days. And so it also is informed by our previous Healthy Human Volunteers study that demonstrated that was the time period to expectation. So the reason for the trial being at length is that it is an informed trial in trying to evaluate those patients with a broad variety of etiology for congenital neutropenia, first identifying them through genetic profiling, and then also identifying their response.
That was the time period to expectation. So the reason for the trial being at length is it is a inform trial in trying to evaluate those patients with a broad variety of etiology for the can get on neutropenia first identifying to genetic profiling and then also identifying their response.
Okay.
And then maybe just.
Lastly, I know, we havent seen obviously any waldenstrom stadia, but.
Lynn Kelly: Okay. And then maybe just lastly, I know we haven't seen any obviously Waldenstrom's data yet, but have you guys given any preliminary thought as to what a registration pathway in this setting might look like? And do you think that because of the targeted nature here that you could get away with, I guess, a single-arm trial, or do you think you would perhaps need to run something more like a small randomized study head-to-head versus BTK?
Let me just given any preliminary thoughts as to what a registration pathway in this setting might look like and do you think that.
Because of the target in nature here that you could get away with I guess, a single arm trial or do you think you would perhaps need to run something more like a small randomized study head to head versus BBK.
Yeah, I think that all those are still a to be determined we really need to get the data from the phase one be trial and were in close communications with the agency about you know expectations, but I'd say, we are evaluating all of our options.
Paula Ragan: Yeah, I think that all those are still to be determined. We really need to get the data from the Phase 1B trial, and we're in close communication with the agency about, you know, expectations. But I'd say we are evaluating all of our options.
Do you think in general there just to add to lens point other companies have always had to run compared or arms with active so that is our current expectation and that's how we're sort of thinking about long term planning. However, the phase one be data will inform how we can approach the agency with anything that might be different from where others.
Stephen Douglas Willey: I do think, in general, though, just to add to Lynn's point, other companies have always had to run comparator arms with ACTIV, so that is our current expectation, and that's how we're sort of thinking about long-term planning. However, the Phase 1b data will inform how we can approach the agency with anything that might be different from where others have come.
Uh huh.
Alright, thanks for taking the questions and congrats no progress.
[laughter].
Your next question Thanks from World.
Operator: Alright, thanks for taking the questions and congrats on all the progress. Your next question comes from our... The next question comes from Arlinda Lee with Canaccord Genuity.
Next question comes from Arlinda, Lee with Canaccord Genuity.
Hi, guys.
Good morning, Arlinda Ari.
Great how are you.
Good.
Congratulations on.
Breakthrough designation I was wondering.
Arlinda Lee: Hey, guys.
Paula Ragan: Good morning, Arlinda. How are you? Great. How are you? Okay.
What data he saw when they granted that as opposed to what we might be seeing in terms of the update and.
Arlinda Lee: Congratulations on the breakthrough designation. I was wondering what data FDA saw when they granted that as opposed to what we might be seeing in terms of the update. And, as well, if you could provide additional color on how enrollment has been going on your Pivotal. Thank you very much.
And as well if you could provide additional color on how enrollment has been going on your capital. Thank you very much.
Hey, Arlinda. This is Glenn so as mentioned earlier the we're excited for the breakthrough designation I think the recognition by the agency that treat say, it's you know applicable to that when being a serious potentially life threatening condition and.
Lynn Kelly: Hey, Orlinda. This is Lynn.
Lynn Kelly: So, as mentioned earlier, we're excited for the breakthrough designation. I think the recognition by the agency that it treats a – it's, you know, applicable to it when it's a serious, potentially life-threatening condition, and, as you spoke, the preliminary clinical evidence. We were able to share with the agency the Phase 2 data, as well as look in depth at some of the infection issues, and that is part of the information we're looking to share later this year, broadly, and that was what their basis of their determination was for the designation.
As you spoke the preliminary clinical evidence we were able to share with the agency the phase two data as well as looking in depth at some of the infection issues and that is part of the information we're looking to share later on this year.
Broadly and that was what their basis of their determination.
Was for the designation.
Lynn Kelly: Okay, great. And then, I guess maybe as a follow-up, how common is testing for the double mutant? I think you've previously mentioned a third or some of the population is double P. And I'm curious how that's been reflected in your enrollment process.
Okay, Great and then I guess, maybe as a follow up how common.
It's tempting for the double.
Thank you previously mentioned third or so the population has doubled.
And I'm curious how that's.
After than your enrollment process, yes, it's been increasingly recognized as a very important marker for how the patient response to treatment and so a number of our centers of excellence the ones that we're working with actually routinely are doing that genetic testing for patients who come in with a primary diagnosis.
Lynn Kelly: Yeah, it's been increasingly recognized as a very important marker for how the patient responds to treatment, and so a number of our Centers of Excellence, the ones that we are working with actually routinely, are doing that genetic testing for patients who come in with a primary diagnosis algorithm for Waldenstrom's, and then also for those patients who may not come in; part of the clinical trial is we include that screening criteria with the genetic testing for the double mutation So it consistently is in the literature is 30-40 percent.
Algorithm for Waldenstrms and then also for those patients who may not come in part of the clinical trial is we include that screening criteria with the genetic testing for the Dublin mutation. So it consistently in the literature is the 30, 40%.
Okay, great. Thank you very much.
Next question comes from Merck from account.
Arlinda Lee: Okay, great. Thank you very much. Our next question comes from Marc Frahm with Calendars. Thanks for taking my questions.
It's thanks for taking my questions.
Just on the.
Yes, I mean, it is early in the enrollment for a CNN faults in terms.
Marc Alan Frahm: First, just on the recognition that it is early in the enrollment for SCN and falls in terms. The updates we expect to get us at the end of the year, I mean, you talked about these trials being designed to, We have discussions regularly about pivotal paths. Is the data that we will see later in the year, you think, going to be enough to have those discussions, or are you going to need more follow-up, more patience than what we're likely to see, given where enrollment is?
The obviously you expect to gives it into the year me you talked about ultimately the trials being designed to.
Have discussions with regulators about pivotal passes.
We will see leader in your you think going to be enough to have those discussions are you going to need more follow up more patients year than what some of them are likely to see a given where enrollment is.
So hey, Mark this is Glenn again, so the expectation for the Waldenstrom trial is 12 to 18 patients.
Lynn Kelly: So, hi Marc, this is Lynn again. So the expectation for the Waldenstrom's trial is 12 to 18 patients. And then remember that's a six month clinical trial currently enrolling patients, and really, the goal of that trial is the dose finding portion, as well as safety with Ibrutinib. Also, the biomarkers are not a burden for the patients to obtain, and easily gotten, and we'll be using that to help inform. But our expectation is to share the preliminary data most likely by the second half of 2020.
And then remember that's a six month clinical trial.
Currently enrolling and the really the goal of that trial is the dose finding portion as well as the safety with Ibrutinib I'm also looking.
The Biomarkers are.
Not a burden for the patient to obtain easily gotten and we'll be using that to help inform but our expectation is to share the preliminary data most likely the by the second half of Twentytwenty.
Marc Alan Frahm: Okay. And then Amy, can you give an update, it wasn't in the press release, just on the status of the next generation of molecules, so 002 and 003, you know, and just working their way towards INDs and other clinics?
Okay and then in can you give an update or it wasn't in the press release, just under 10 status of the next generation molecule. So here's your two answers your three.
No just working their way towards signed piece and the clinic.
Yeah. Thanks, Marc I appreciate the interest so OTI went out with three or making nice progress towards I. Indeed, enabling studies O. Three is sort of a leader in APAC at this point and we do you expect Junichi I Indeed, enabling studies this year.
Paula Ragan: Yeah, thanks, Mark. I appreciate the interest. So, OO2 and OO3 are making nice progress towards IND-enabling studies. OO3 is sort of the leader in the pack at this point, and we do expect to initiate IND-enabling studies this year.
Okay, great. Thank you.
Marc Alan Frahm: Okay, great. Thank you.
Our next question comes from drove beauty with Citi.
Operator: Our next question comes from Joel. Hi, thanks for taking the questions. The first one is on Lyme syndrome. Could you discuss the patient identification efforts currently used for both the trial as well as what's in the community and could be used upon approval?
Hi, Thanks for taking the questions. The first one is on the one syndrome could you discuss the patient identification efforts.
Currently used for both the trial.
Well, it's what you know in the community and I couldn't could be used upon approval.
Joel: Sure. Thanks for the question.
Sure. Thanks for the question. So there's different approaches for patient identification in terms of those for the trial and we have sort of obviously, our broad network of clinicians and sites that have been instrumental in building the final to support patient enrollment. So I think that's it.
Paula Ragan: So, there are different approaches for patient identification. In terms of those for the trial, we have sort of, obviously, our broad network of clinicians and sites that have been instrumental in building the funnel to support patient enrollment. So, I think that's sort of a nearer-term approach that is very relationship-driven, and we're in good shape to complete enrollment by the end of the year through those mechanisms. In the longer term, sort of a broader sense in terms of registries and preparing for our hopeful ultimate approval for Maverix X4, we've been taking similar approaches as other rare disease companies where we're working with existing genetic databases, we' So, we'll be able to give an update on some of that at the April 7th Analyst Day, and we do feel, you know, it continues to support our current guidance around the 1,000 genetically confirmed WIMP patients in the U.S., and we certainly feel like there's potential beyond that.
For the but I sure nearer term approach that is very relationship driven and we're in good shape to complete enrollment by the end of the year through those mechanisms in the longer term sort of broader sense in terms of registries and preparing for all our hopeful ultimate approval for matter, except for we've been taking so.
More approaches to as other rare disease companies, where we're working with existing genetic data bases or doing electronic medical Records research primary market research as well as using some targeted a field force efforts with our MSL. So we'll be able to give an update on some of that's at the April 7th a analyst day.
And we do you feel you know it continues to support our current guidance around the thousands genetically confirmed when patients in the U.S.
And certainly feel like theres potential beyond that.
Great and then a question on.
Joel: Great. And then a question on dosing and differences in dosing between indications. Could you give a sense of what you anticipate the highest dose or dose could be for Waldenstrom's compared to other indications like WIM and SCN? Or is it too early to have a sense of that?
Dosing and differences in dosing between indications.
Did you give a sense of what you anticipate the highest dose or dosing could be for waldenstrom compared to other indications like when I see on or is it too early to have a sense of that.
Hey, Joe its Lynn I think it's too early to have a sense of I think we chose the dose for the Walton from the won some says that dose escalation. The 200 400 600 and in the when we use the phase two data to inform using the 400 doses the responsiveness for those patients that were on trial.
Lynn Kelly: Hey, Joel. It's Lynn. I think it's too early to have a sense of that.
Joel: I think we chose the dose for the Waldenstroms. The Waldenstroms is the dose escalation, the 200, 400, and 600. And in the WIM, we used the Phase 2 data to inform using the 400 dose as the responsiveness for those patients that were on trial.
Operator: Great. Got it. Thank you. Our next question comes from Swayampakula Ramakanth with AC Wainwright.
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Great got it thank you.
Our next question comes from Swayampakula, Ramakanth AC rig <unk> Wainwright.
Thank you. This is okay from two end right.
Swayampakula Ramakanth: Thank you. This is R.K. from H.P. Wayne-Ray. Good morning, Paula. Good morning, Len. Regarding your Analyst Day on April 7th, what should we expect to be discussed there? And I think it's going to be webcast too, right?
Good morning, Paula Good morning Lynn.
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Regarding your analyst day on April seven.
What should we expect.
The discuss there.
And I think it's going to be that us too right.
Paula Ragan: Correct. So, the expectation is that it's focused on Wim Syndrome. We will share a patient experience via video so people can have a first-hand understanding of what it feels like to live with Wim Syndrome. We will share our KOL's views and experiences treating the disease as well as some of his experiences with our Phase 2 study. And then we will be providing guidance on some additional market research around prevalence.
Correct I said that expectation is that it's focused on when syndrome.
We will share a patient experience via video so people can have a first hand understanding of what it feels like to live with when syndrome I, we all share our care wells of use and experiences treating the disease as well as some of his experiences with our phase two study and then we will be providing guidance on some additional market.
Research around prevalence.
Thank you for that and then.
Swayampakula Ramakanth: Thank you for that. And then, regarding the pivotal study, what could we hear from you in terms of data while we wait for this study to really get to completion in the second half of 2021? What sort of updates could we get from you, folks?
Regarding the.
We will study.
Walked.
What could we hear from you in terms of data.
Well they told the study do you.
Really get to completion in the second have tended to do on.
What sort of updates.
We could be.
Lynn Kelly: So, as it's a prospective randomized double blind trial, there's no expectation of release of that data until the really completion of the trial. And then four, we will be sharing data around phase two and the extension portion of phase two in the 2020 time period.
Good for you folks.
So so.
As it's a prospective randomized double blind trial, there is no expectation of release of that data until really completion of the trial.
And then for we will be.
Sharing data around the phase two and the extension portion of the phase two in the 2020 time period.
Okay. Thank you. Thank you for taking the questions.
Our next question comes from our trailer with Oppenheimer.
Swayampakula Ramakanth: Okay, thank you for taking the questions. Our next question comes from Alex Heller with Oppenheimer. Hi, good morning. This is Alex Peller on behalf of Leland Groeschel. Thanks for taking my question. Are you able to share any updates on the diagnosis rate through your NVTA partnership?
Hi, good morning, Alec smaller on for Leland Gershell. Thanks for taking my question are you able to share any update on the diagnosis rate through your in detail partnership.
Thanks for the question worse I still in progress with.
Oh, leading all the data and so I think at this point, we just want we're not going to give guidance specifically on the results for any Teva, we certainly recognize that's an important tool and the overall diagnosis of SDN and win so we'll provide guidance on when you can expect that at a forthcoming discussion.
Alex Heller: Thanks for the question. We're still in progress with Thank you.
Paula Ragan: Okay, thanks. And then, any update on your thoughts on the EU's commercial strategy?
Okay. Thanks, and then any update on your thoughts on E commercial strategy.
Sure. So I think again as a rare disease focused company, we intend to globally commercialize in the primary Immunodeficiencies I, certainly when NFC and fit very nicely from our strategic sort of call point and synergy perspective, and then with respect to walnuts Troms again its.
Paula Ragan: Sure. So I think, again, as a rare disease-focused company, we intend to globally commercialize our product for primary immunodeficiencies. Certainly WIM and SCN fit very nicely from a strategic sort of call point and synergy perspective. And then, with respect to Wallenstroms, again, it's a relatively targeted specialist group, so our intention at this point is to go alone, but we'll always be considering how to best grow the company as the data unfolds and as we better understand the global commercial landscape.
A relatively targeted.
Ashland's group so our intention at this point is to go alone, but we will always be considering how to best grow the company I asked the d. it unfolds and as we better understand the global commercial landscape.
Okay perfect. Thanks, so much.
Alex Heller: Okay, perfect. Thanks so much.
Our next question comes from retrofitted with Roth Capital Partners.
Operator: Our next question comes from Zagraj Jhala with Rothkamp. Good morning. Just had a couple of questions. I think the first one is, you know, for Waldenstrom. I haven't been able to find any details on the study, but just had a question about the potential sequencing of ibrutinib and Mavirex IV. Are you, you know, playing with that in terms of the sequencing of events to prevent any kind of resistance?
Good morning, just had a couple of questions I think the first one is you know for well just and I haven't been able to find any details on they study, but he's had a question about the potential sequencing of the button that then memorex and for our you know playing with that in terms at the sequencing of events to prevent.
Any kind of resistant and then second question is that the launching of study is enrolling patients pretreated with the boot Ned I would imagine that should be easier to promote relative to win so any updates on enrollment there and then lastly, any learnings from they deans luggage and study and I know you said.
Zagraj Jhala: And then the second question is that the Waldenstrom study is enrolling patients pretreated with ibrutinib. I would imagine that should be easier to enroll relative to WIM, so any updates on the enrollment there? And then lastly, any learnings from Bayeudine's Waldenstrom study? And I know you said that you're looking forward to 2H20 for the readout of the study, at least for PK and biomarker. I was wondering if you were aiming for any clinical meetings in the second half of the year.
You are looking for two to age 20 for what the readout of the study at least for P. Chem biomarker I was wondering if you're aiming for any clinical meeting in the second half the here.
Lynn Kelly: So I'm going to try to answer all your questions going forward. So, first of all, to clarify, this patient population, the population for the Waldenstrom's trial, is both de novo patients and recurrent refractory, but these patients would not have seen abrutinib prior to our trial. And so that is an important point. We are keeping the abrutinib dose steady, and the dose escalation is for Mavarixa 4. And so we are well aware of the expectations for that, and that's the design of the trial. And then we are looking to share the preliminary results in the second half of 2020, and we're not commenting on any specific targeted meeting. We're in the process of enrollment, and so it would be premature to say that.
So my try to answer all your [laughter] going forward. So I think first of all to clarify this patient did population for the Waldenstrms trial is both denovo patients and recurrent refractory, but patients would not have seen a brutal but price.
Our to our trial and so that is an important point, we are keeping the abruzzi of dose steady and we are the dose escalation is for Mavericks before and so we are well aware of.
The expectations for that and we have that's the design of the trial and then we are looking to share the results a preliminary results at second half of 2020, and we're not commenting on any specific targeted meeting we're in a process of enrollment and so it would be premature to say that.
[noise] booms and that does have a quick clarification I think you said that after the R&D, perhaps you'll be providing additional updates on the Lin study just rent I understand the sequence that that data is not going to come at the R&D day, but that you know a little bit later.
Zagraj Jhala: And I just have a quick clarification. I think you said that after the R&D, perhaps you'll be providing additional updates on the WIM study. Just wanted to understand the sequence of that data is not going to come out on the R&D day but instead, you know, a little bit later.
Yes, so there'll be no data at the no new data at the analyst day on April 7th mid year as Lynn mentioned, we do have additional data that someone raised the question about what did the FDA get to feed to granted breakthrough. So we intend to share that information with respect to infection.
Paula Ragan: Yes, so there will be no new data at Analyst Day on April 7th. Mid-year, as Lynn mentioned, we do have additional data that someone raised the question about what the FDA got to see to grant us breakthrough, so we intend to share that information with respect to infection rates and additional clinical assessments to help the general public understand the full dataset by mid-year this year.
Great.
And additional clinical assessments to help the general public understand the de at full data set by midyear this year.
Paula Ragan: Thanks, Paula. Sure. And I'm not asking any further questions at this time. I turn the call back over to Paula.
Oh.
Sure.
And I'm not showing any further questions at the start more through Mccall brokered Apollo.
Great well. Thank you so much everyone. We really appreciate your time today and if you have any further questions. Please do not hesitate to reach out to Kansas, We'll do our best to always support your interest in X four. Thank you so much and have a great day.
Paula Ragan: Great. Well, thank you so much, everyone. We really appreciate your time today. And if you have any further questions, please do not hesitate to reach out to Candice. We'll do our best to always support your interest in X4. Thank you so much, and have a great day.
Operator: Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.
Ladies and gentlemen. This concludes todays presentation you may now disconnect remember wonderful day Goodbye.