Q4 2021 X4 Pharmaceuticals Inc Earnings Call

Operator: Greetings and welcome to X4 Pharmaceuticals Third Quarter Financial and Operating Results Conference Call. At this time all participants are in a listen-only mode.

Greetings and welcome to explore pharmaceuticals third quarter financial and operating results conference call. At this time all participants are in a listen.

Only mode a question and answer session will follow the formal presentation. As a reminder, this conference call is being recorded it is now my pleasure to introduce your host Dr.

Operator: This question and answer session will follow the formal presentation. As a reminder, this conference call is being recorded. Now, my pleasure.

Glenn Shulman: Glenn Shulman, Head of Investor Relations. Thank you, Operator, and good morning, everyone. Presenting on today's call will be X4's Chief Executive Officer, Dr. Paula Ragan, and the company's Chief Financial Officer, Adam Mostafa. Following some prepared remarks by each, we will then open the call to your questions, where we'll also be joined by our Chief Scientific Officer, Art Tavares, Chief Medical Officer, Diego Cadevid, and Chief Operating Officer, Mary Dubiasa. As a reminder, on today's call, X4 will be making forward-looking statements regarding regulatory and product development plans, as well as research activities. These statements are subject to risks and uncertainties that may cause actual risks to differ from those forecasted.

Head of Investor Relations. Please begin.

Thank you operator, and good morning, everyone.

On today's call will be exports, Chief Executive officer, Dr. Paula Ragan, and the company's Chief Financial Officer, Adam itself up.

Following some prepared remarks by each we will then open the call to your questions are where we'll also be joined by our Chief Scientific Officer are terrorists Chief Medical Officer, Diego, how does it and Chief operating Officer Mary Dubiosity.

As a reminder, on today's call export will be making forward looking statements regarding regulatory and product development plans as well as research activities. These statements are subject to risks and uncertainties that may cause actual risks to differ from those forecasted a description of these rights can be found next words, most recent filings with the SEC, including <unk>.

Our Form 10-K being filed today and now I'd like to turn the call over to Paula Ragan, President and CEO Paula.

Glenn Shulman: A description of these rights can be found in X4's most recent filings with the SEC, including our Form 10-K being filed today. And now I'd like to turn the call over to Paula Ragan, President and CEO. Paula.

Paula Ragan: Thanks, Glenn, and thank you, everyone, for joining us on the call this morning. Before we get started, I did want to officially introduce our new Vice President of Investor Relations and Corporate Communications, Glenn Shulman, who you just heard from. He has a Master's in Public Health and a Pharm.D. and extensive public life sciences company experience leading successful investor relations and corporate communications teams and programs. Glenn joined us in mid-November and has been a great addition to the team. Welcome Glenn. Plyclein I was an important year for X4.

Thanks, Glenn and thank you everyone for joining us on the call. This morning.

Before we get started I did want to officially introduce our new Vice President of Investor Relations and corporate Communications, Glenn Schulman, who you just heard from he is a masters in public health and our Pharm D and an extensive public life Sciences company experience, leading successful Investor Relations and corporate communications teams and program.

Glenn joined US in mid November and has been a great addition to the team welcome Glenn.

Paula Ragan: A year of execution across our multiple ongoing clinical trials and significant progress in advancing our lead candidate, Mavericks IV, closer to patients and needs. A year of execution across our multiple clinical trials and significant progress in advancing our lead candidate, Mavericks IV, closer to patients and needs. And importantly, we expect 2022 to be a pivotal year for the company, a year of clinical results that will shape the future of X4 for years to come.

Slide 21 was an important year for <unk> for a year of execution across our multiple ongoing clinical trials and significant progress in advancing our lead candidate Mavericks before closer to patients in need.

And importantly, we expect 2022 to be a pivotal year for the company a year of clinical results that will shape the future of X for for years to come.

Paula Ragan: During 2021, not only did we complete enrollment in the Pivotal Phase 3 trial of Mavericks 4 and Wimson Drown for the 4 Wim trial, but we also enrolled enough patients in our 2 earlier stage trials to achieve proof of concept for Mavericks 4 and 2 additional rare disease indications with many thousands of patients that have great medical need for additional treatment. Chronic Neutrupinia, and Waldron, Michael Zrobio-

During 2021, not only do we complete enrollment in the pivotal phase III trial of Maverick's flora and whim syndrome.

For the four women trial, but we also enrolled enough patients in our Q earlier stage trials to achieve proof of concept for Maverick before and two additional rare disease indications with many thousands of patients that have great medical need for additional treatment.

Neutropenia, and Walton from snack with Robbie linear.

Paula Ragan: Thirty-one adults and pediatric patients have been enrolled in the FORWIM trial, which was originally designed to enroll 18 to 28 patients. As you know, this clinical trial is evaluating the safety and efficacy of a single daily oral dose of Maverick Support in patients with Wim Syndrome, a rare genetic immunodeficiency disorder caused by gain-of-function mutations to the CXCR4 receptor. The disease is characterized by HPV-associated warts, hypogamialoglobulinemia, multiple types of infections, and myelocoshexis, which causes leukopenia and neutropenia in most patients, reducing the body's ability to mount a healthy immune response.

31, adult and pediatric patients have been enrolled in the four whim trial, which was originally designed to enroll 18 to 28 patients.

As you know this clinical trial is evaluating the safety and efficacy of a single daily oral dose of Maverick Sephora in patients with <unk> syndrome, a rare genetic immunodeficiency disorder caused by gain of function mutations to the <unk> four receptor.

The disease is characterized by HPV associated works hypokalemia like globular anemia, multiple types of infections, and Milo cathexis, which causes leukopenia and neutropenia and most patients reducing the body's ability to Mount a healthy immune response.

Paula Ragan: Results from the ongoing open-label extension of our Phase 2 clinical trial of Mavericks for and when patients continue to support this indication, with data showing durable increases in neutrophils, lymphocytes, and monocytes, decreased Frequency, Severity, and Duration of Infections, Fewer Hospital Doctor Visits, and Sustained Improvement in Warts. FABRIX4 continued to be well tolerated over a median treatment duration of We continue to anticipate top-line data from the 4 WHM trial in the fourth quarter of 2022.

Results from the ongoing open label extension of our phase two clinical trial of Mavericks for it and when patients continues to support the syndication with data showing durable increases in neutrophil lymphocyte, Ken Monocyte <unk>.

Decreased frequency severity and duration of infections fewer hospital doctor visits and sustained improvement in works.

Mavericks for a continued to be well tolerated over a median treatment duration of almost 150 weeks.

We continue to anticipate topline data from the four women trial in the fourth quarter of 2022.

Paula Ragan: We ended last year with our largest ever presence at a scientific meeting, the Annual Meeting of the American Society of Hematology, or ASH, and we held a company virtual seminar immediately following with several key thought leaders in the industry. Our posters and abstracts at the AFT meeting contained a broad array of both clinical and scientific data. Data that we believe not only further establishes X4 as a leader in the CXCR4-related research space but also supports the broadening scope of the clinical potential of Maverick-CF4 due to its ability to selectively inhibit CXCR4.

We ended last year with our largest ever present at a scientific meeting.

Annual meeting of the American Society of Hematology or Ash, and we held the company virtual seminar immediately following several key thought leaders in the industry.

Our posters and abstracts at the Ash meeting contained a broad array of both clinical and scientific data.

Data that we believe not only further establishes export as a leader in the <unk> related research space.

Also supports the broadening scope of the clinical potential of Maverick before due to its ability to selectively inhibit CXC are for.

Paula Ragan: At the meeting, we shared data demonstrating the effect of Maverix 4 across multiple disease states, multiple cell types, and over chronic periods of dosing. For example, one of our posters showed for the first time that Maverick 4 is able to raise total counts of all the key white blood cells necessary to mount an appropriate immune response across a wide spectrum of diseases over both short and long-term treatment periods. Data were presented from ongoing clinical trials in Waldenstrom's macroglobulinemia, clear cell renal cell carcinoma, Wim Syndrome, and, for the first time, early data from our ongoing Phase 1b trial in patients with chronic neutropenia.

At the meeting we shared data demonstrating the effect of maverick's for across multiple disease states multiple cell types and over a chronic periods of dosing.

One of our poster showed for the first time that Maverick sport is able to raise total counts of all the cute white blood cells necessary to Mount an appropriate immune response across a wide spectrum of diseases over both short and long term treatment period.

Data were presented from ongoing clinical trials and wall tiles macro globular anemia clear cell renal cell carcinoma whim syndrome and for the first time early data from our ongoing phase <unk> trial in patients with chronic neutropenia.

Paula Ragan: These data demonstrated that mavericks of work broadly increased white blood cells and mutual accounts, anywhere from 2 to 6 fold, across all indications, as well as in healthy subjects. Early data from our Phase 1b clinical trial in chronic neutropenia mirrored these results, with demonstrated elevations in white blood cells and absolute neutrophil, lymphocyte, and monocyte counts across the first four patients enrolled in the trial. As a reminder, chronic neutropenia refers to a condition of sustained or recurrent abnormally low neutrocell counts lasting at least three months.

These data demonstrated that maverick before a broadly increase white blood cells and neutrophil counts anywhere from two to six fold across all indications as well as in healthy subjects.

Early data from our phase <unk> clinical trial in chronic neutropenia mirrored these results with demonstrated the elevations in white blood cells, and absolute neutrophil lymphocyte and monocyte counts across the first four patients enrolled in the trial.

As a reminder, chronic neutropenia reversed with condition, a sustained or recurrent abnormally low neutrophil counts lasting at least three months it's.

Paula Ragan: It's estimated that 6 in 10,000 people have chronic neutropenia, which can be present in a variety of severities, such as Mild, Moderate, or Severe, and can increase the risk of serious and recurrent infections in patients. Enrollment in our Phase 1b trial continues, with additional data expected in the second or third quarter of 2022. It was a compelling set of consistent responses, irrespective of disease state and irrespective of CXCR4 mutation status. And in aggregate, have encouraged us to think much more broadly about how Maverix work could impact larger numbers of patients with primary immunodeficiencies.

It's estimated that six and 10000 people have chronic neutropenia, which can be present in a variety of severity.

Mild moderate or severe.

And can increase the risk of serious and recurrent infections in patients.

Enrollment in our phase one B trial continues with additional data expected in the second or third quarter of 2022.

It was a compelling set of consistent responses irrespective of disease state and irrespective of <unk> mutation status.

And in aggregate have encouraged us to think much more broadly about how maverick sport could impact larger numbers of patients with primary immunodeficiency.

Paula Ragan: Whether caused by CX-04 mutations as in the case of limb syndrome, or via antagonism of the wild types, CX-04 signaling pathway, and many other cellular inhibitions. We also presented results from our ongoing Phase 1b clinical trial in people with Waldenstrom's macroglobulinemia. A rare B-cell lymphoma.

They are caused by <unk> mutations as in the case of whim syndrome.

Or via antagonism of the wild type <unk> signaling pathway and many other cellular deficiencies.

We also presented results from our ongoing phase <unk> clinical trial in people with wall in China's macro globule anemia.

A rare b cell lymphoma.

Paula Ragan: At low 200 mg and mid-level 400 mg dosing of Mavrexivir combined with the BTK inhibitor imbrutinib, the median treatment duration was 272 days. As a reminder, this Phase 1b trial is designed to demonstrate safety, dose, and elucidate proof of concept of Maverick support in people with Waldenstrom who have significant unmet needs resulting from mutations to both their MYD8H and CX The data showed a 100% overall response rate in the 10 evaluable double mutation patients.

At low 200 milligram and mid level 400 milligram dosing of Maverick before combined with the V. TK inhibitor in brewing at the median treatment duration of 272 days.

As a reminder, this phase <unk> trial is designed to demonstrate safety dose and elucidate proof of concept of Maverick before and people with Walden strong with significant unmet needs, resulting from mutations to both <unk> and <unk> genes.

The data showed a 100% overall response rate and the 10 evaluable double mutation patients.

Paula Ragan: Sustained decrease in serum IgM levels and a trend towards normalization of hemoglobin. We also announced this morning that 600 mg of Maverix X4 was cleared from the ongoing study. All eligible patients in cohorts A and B for the low and mid-level cohorts are now being dose escalated to receive 600 mg of Maverix XIV once daily in combination with Brutinib. We expect to report updated data from this trial during the second half of the year.

Staying that decrease in serum IGN levels, and a trend towards normalization of hemoglobin levels.

We also announced this morning that 600 milligram dose of Maverick before was cleared in the ongoing study.

All eligible patients in cohorts, a and b or the low end mid level cohorts are now being dose escalated to receive 600 milligrams of Maverick before once daily in combination with Ibrutinib.

We expect to report updated data from this trial during the second half of the year.

Paula Ragan: At ASH last December, we also announced that our research efforts had led to the discovery of several novel Wim-causing CXBR4 mutations, the incidence of which further strengthens our confidence that there are more than 3,500 WIMP patients in the U.S. alone. More detailed data on one of these mutations, the D84H mutation, was just presented at the American Academy of Allergy, Asthma, and Immunology, or Quad AI, meeting in late February. The poster for this is available on our website.

At Ash last December we also announced that our research efforts have led to the discovery of several novel women, causing <unk> mutation.

The incidence of which further strengthens our confidence that there are more than 3501 patient in the U S alone.

Detailed data on one of these mutations the day 84 H mutation was just presented at the American Academy of allergy asthma and immunology.

Or quite AI meeting in late February the poster for this is available on our web site.

Paula Ragan: Looking forward, our participation at major medical conferences does continue in 2022, where we are working hard to educate the medical community and raise awareness of WIM. At the upcoming 2022 Clinical Immunology Society or CIS conference, we'll present for the first time another recently identified novel WIM variant, the S-341-1-3.

Looking forward our participation at major medical conferences continues in 2022, where we are working hard to educate the medical community and raise awareness of win at the upcoming 2022 clinical Immunology Society are Cif conference well presented for the first time. Another recently identified novel win variant.

The S 341 wide variation.

Paula Ragan: This, combined with the D84H indication, are just two of the many Novel 1 variants that have been sequenced, characterized, and published in the literature stemming from our world-class research center in Vienna. Next month at the AACR conference, our preclinical team will be presenting new data demonstrating the additive to synergistic activity of Maverix IV when combined with any BTK inhibitor, including Xanibrutinib and With that update complete, I would like to take a little time today to share some insights into our commercial approach as we near our first Phase 3 clinical data in Maverick for the treatment of Lymph Syndrome.

This combined with the data for each location are just few of the many novel wind variance that had been sequence characterize and published until literature stemming from our World Class Research Center in Vienna.

Next month at the ACR conference, our preclinical team will be presenting new data demonstrating the additive to synergistic activity of Maverick score when combined with any PK inhibitor, including zandi brute nib and agree with him.

With that update complete I would like to take a little time today to share some insights and our commercial approach is linear our first phase III clinical data and Maverick before for the treatment of whim syndrome.

Paula Ragan: The first is our early engagement with patient communities through patient advocacy. Patient voices are at the center of all decisions we make at X4. Early in the Mavericks clinical development process, we appointed a vice-president, patient advocacy, who engaged with patient advocacy groups long before entering the Phase 3 trial, which enabled us to understand the diverse disease journeys and unmet needs of our patients. We have worked closely with patient advocacy groups all along to develop disease awareness materials and other resources to help educate patients on testing resources, disease presentations, access to medical experts, and treatment options available or in clinical development.

The first is our early engagement with patient communities through patient advocacy.

Voices are at the center of all decisions, we make at X for <unk>.

Early in the Maverick for our clinical development process, we appointed a vice president of patient advocacy.

So engaged with patient advocacy groups long before entering the phase III trial, which enabled us to understand the diverse disease journeys and unmet needs of our patients.

We're closely with patient advocacy groups, all along to develop disease awareness materials and other resources to help educate and testing resources disease presentation access to medical experts and treatment options available are in clinical development.

Paula Ragan: The second is our educational support and access to genetic testing to improve diagnosis. As you likely know, diagnosis and patient identification are the main challenges for rare diseases. Due to the heterogeneous symptom presentation and lack of physician awareness, Sym Syndrome is often difficult to diagnose.

The second is our educational support and access to genetic testing to improve diagnosis.

As you likely know diagnosis and patient identification is the main challenges for rare disease.

These are the heterogeneous symptom presentation and lack of physician awareness.

Syndrome is often difficult to diagnose this leads to long diagnosis journeys and delayed access to the symptomatic treatments. The current standard of care.

Paula Ragan: This leads to long diagnosis journeys and delayed access to the symptomatic treatments of the current standard of care. People with Wim Syndrome often visit numerous medical specialties before being diagnosed. As we've discussed previously, we sponsor a no-charge genetic testing and counseling program, Task Forward, for individuals who might carry mutations associated with congenital neutropenia, including Lyme syndrome, to aid in patient identification and to help bring patients one step closer to an accurate diagnosis.

People with whim syndrome, often visit numerous medical specialties before being diagnosed.

As we've discussed previously we sponsor a no charge genetic testing and counseling program path forward for <unk> individuals, who liked carrying mutations associated with congenital neutropenia, including limb syndrome.

Eight in patient identification and to help bring patients one step closer to an accurate diagnosis.

Paula Ragan: We also employ the use of artificial intelligence and machine learning tools to enhance our understanding of the prevalence and burden of disease. Women are thought to be under diagnosed due to the absence of an international classification of disease or ICD-10 code, as well as inconsistent coding for key symptoms. We have utilized artificial intelligence and machine learning platforms to identify patients with WIM look-alike clinical phenotypes that might have been previously undiagnosed due to inconsistent symptom presentation.

We also employ the use of artificial intelligence and machine learning tools to enhance our understanding of the prevalent and burden of disease.

Women are thought to be under diagnosed due to the absence of an international classification of disease or ICD 10 code as well as inconsistent coding for key symptoms do you view that.

Artificial intelligence and machine learning platforms to identify patients with women look like clinical phenotypes that might have been previously undiagnosed due to inconsistent symptom presentation.

Paula Ragan: As we talked about last year, this space of whim is like a puzzle with our ongoing research and that of the physician, scientist, and teaching communities. There's increasing clarity of the understanding of the disease as it continues to evolve, as is often the case with many rare diseases. [inaudible] We have also assembled a strong medical affairs team. Building a specialized team geared towards physician education and creating partnerships to increase awareness of Lyme syndrome is a critical bit to Achieving Our Goals.

As we talked about last year this space of whim, if like a puzzle, but with our ongoing research and that of the physician scientists and patient communities.

Increasing clarity as the understanding of the disease continues to evolve.

As is often the case with many rare diseases.

We have also assembled a strong medical affairs team building a specialized team geared towards physician education, and creating partnerships to increase awareness of whim syndrome is a critical bitch to.

To achieving our goals.

Paula Ragan: Collectively, we feel passionately about empowering medical professionals and their patients to understand their unique journeys so that they can get answers and find available treatments. Lastly, and as we just mentioned, we continue to conduct research on the underlying genetics of LAMs. We have built strong in-house research programs that leverage world-class collaborations to advance bench-to-bedside research. By continuing to establish correlations between clinical presentation and new genetic variants associated with WIM, we can improve our ability to identify undiagnosed patients, including those who may potentially benefit from Mavericks of our treatment and the event-eating to prove it. Of course, building a sustainable rare abuse business is not fully rooted in supporting patients in need.

Collectively we feel passionately about empowering medical professionals and their patients to understand their unique journeys. So that they can get answers and find available treatments.

Lastly, and as we just mentioned we continue to conduct research on the underlying genetics of Lam.

We have built strong in house research programs that leverage world class collaborations to advance the bench to bedside research.

By continuing to established correlation between clinical presentation, and new genetic variance associated to win we can improve our ability to identify and diagnose patients, including those who may potentially benefit from Maverick Safari treatments in the event <unk> approval.

Of course building a sustainable rare disease business is not solely rooted in supporting patients and physicians as.

Paula Ragan: There's much more needed beyond that that we need to deliver on, and we are well on our way. We have made great progress in adding leadership to the company with our VP of U.S. Commercial and our new board director, both with significant life science commercialization experience. More key hires, including a chief commercial officer, are slated for 2022.

There's much more need it beyond that.

With that we need to deliver on and we are well on our way.

We've made great progress in adding leadership to the company with our VP of U S commercial and our new board of director, both with significant lifetime commercialization experience.

More key hires including a chief commercial officer are slated for 2022.

Paula Ragan: In terms of our ultimate commercial product, we have taken the appropriate steps in terms of registration and validation batches to support our NDA filing and are advancing our work to support Mavericks for future commercial trade dress and third-party logistics providers to enable a successful U.S. market. Finally, and importantly, given the disease-modifying impact that Maverick 4 may have on this rare Wimps Syndrome population. Baring Asian Pears, with research and education in the US and key European territory.

In terms of our ultimate commercial product you have taken the appropriate steps in terms of registration and validation batches to support our NDA filing and are advancing our work to support maverick towards future commercial trade dress and third party logistic providers to enable a successful U S launch.

Finally, and importantly, given the disease modifying impact that Mavericks, where it may have on this rare whim syndrome population.

We are engaging payers with research and education in the U S and key European territories.

Paula Ragan: [inaudible] All of these platforms and initiatives that are working in concert to enable us to be ready to deliver our patients and in the event of our first approval. With that update, I now turn it over to Adam to discuss results for the quarter before we open up the call for questions. Adam?

All of these platforms and initiatives are working in concert to enable us to be ready to deliver for our patients in the event of our first approval.

With that update I'll now turn it over to Adam to discuss results for the quarter before we open up the call for questions Adam.

Adam Mostafa: Thanks, Paula, and thanks to all of you on the call. As presented in our press release this morning, I will summarize our financial activities and results for the fourth quarter ended December 31st, 2021. At the end of 2021, X4 had $83.1 million in cash, cash equivalents, and restricted cash.

Thanks, Paul and thanks to all of you on the call today.

As presented in our press release. This morning, I will summarize our financial activities and results for the fourth quarter ended December 31 2021.

At the end of 2021.

Four at $83 1 million in cash cash equivalents and restricted cash.

Adam Mostafa: We continue to expect that our cash and cash equivalents will fund our operations. Welcome to the fourth quarter of 2022. Research and development expenses were $12.2 million for the fourth quarter ended December 31, 2021, as compared to $12.3 million for the comparable period in 2020. General and administrative expenses were $7.1 million for the fourth quarter ended December 31, 2021, as compared to $5.4 million for the comparable period in 2020. Finally, X4 reported a net loss of $30.2 million for the fourth quarter of 2021, which included approximately $11.4 million in non-cash expenses, of which $9.8 million is an impairment of goodwill charge.

We continue to expect that our cash and cash equivalents will fund our operations into the fourth quarter of 2022.

Research and development expenses were $12 2 million for the fourth quarter ended December 31 2021.

As compared to $12 3 million for the comparable.

Period in 2020.

General and administrative expenses were $7 1 million for the fourth quarter ended December 31, 2021, as compared to $5 4 million for the comparable period in 2020.

Finally, <unk> reported a net loss of $30 2 million for the fourth quarter of 2021, which includes approximately $11 4 million in non cash expenses of which $9 $8 million as an impairment of goodwill charge.

As compared to a net loss of $18 4 million for the comparable period in 2020.

Operator: As compared to a net loss of $18.4 million for the comparable period in 2020. We'll now open up the call for your questions. Operator?

We will now open up the call for your questions operator.

Operator: Thank you. And as a reminder, to ask a question, simply press star 1 on your telephone. To withdraw the question, press the pound or hash key.

Thank you and as a reminder to ask a question simply press star one on your telephone to withdraw your question press the pound or high ski one moment, while we compile the Q&A roster.

Stephen Willey: One moment while we compile the answers. We have a question from Stephen Willey with Diffle, Your Lanny Soul. Yeah, good morning, guys. Thanks for taking the question. I guess as you think about the WIM data, I know we get the top line disclosure in the fourth quarter. You'll subsequently be talking to payers and getting a sense of what reimbursement might look like.

We have a question from Stephen Willey with Stifel. Your line is open.

Yes, good morning, guys. Thanks for taking the question.

I guess as you think about the wind data.

We get the topline disclosure.

Disclosure in the fourth quarter.

You subsequently be talking to payers and.

Getting a sense of.

But what reimbursement might look like just curious as how that information.

Stephen Willey: Just curious, as you know, how that information that you get from payers and reimbursement will inform, if at all, the target patient population that you choose to pursue in chronic neutropenia. I guess, is there a chance here that you just select the more severe patients? i.e.

That you get from payers and reimbursement.

We'll inform you if at all the target patient.

Population that you choose to pursue.

Sonic neutropenia.

I guess is there a chance here that you just select the more severe patients.

Paula Ragan: those that have more than two infection events a year, those on chronic GCSF. Just wondering how you're thinking about how the wind data shapes the TPP for chronic nature. Hi, Steve. Good morning.

Those that have more than two infection events a year those on chronic G CSF.

Just wondering how youre thinking about how the wind data shapes the TPP four.

For chronic neutropenia.

Paula Ragan: Thank you for the question. I think we kind of think about it on almost two different axes. There's sort of a patient number question, which I think the rare disease community is familiar with in terms of the ability to gain, you know, appropriate value propositions for these ultra-orphan diseases, and then it kind of sometimes correlates with patient numbers. So, with WIM, we've tested that, and we actually think we have a fairly broad range of patient numbers that certainly supports the current WIM numbers that we have and actually well beyond that.

Hi, Steve Good morning. Thank you for the question. So I think we kind of think about it almost on few different axes, there sort of a patient number question, which I think the rare disease communities familiar with in terms of the ability to to gain.

Appropriate value propositions for these ultra orphan diseases, and then it kind of sometimes correlate with patient numbers.

Paula Ragan: So, as additional patients and additional indications come on, we don't think that that would have any sort of pricing impact on how we go out with WIM. So, we don't think that with chronic neutropenia's larger numbers, it would impact our overall pricing strategy. And then I think you're correct.

So with when we've tested that and we actually I think we have a fairly broad with the patient numbers that certainly supports the current women numbers that we have and actually well beyond that so as additional patients and additional indications come on we don't think that that would have any sort of pricing impact on how we go out with whim. So we don't think.

Paula Ragan: I mean, ultimately, what we're trying to do is answer a high unmet need. We've shared already today that there are about 5,000 patients with chronic neutropenia that have these very severe, we call them serious infection events, at least two per year or more. And certainly, in some ways, those patients are as severe, if not more severe, than those that we've seen with WIM syndrome.

With chronic neutropenia at larger numbers.

It would impact our overall pricing strategy.

And then I think Youre correct I mean, ultimately what we're trying to do is answer a high unmet need and we've shared already today that there's about 5000 patients with chronic neutropenia that have these very severe or we call them serious infection events at least two per year or more and certainly in some ways. Those patients are at severe if not more severe than.

Paula Ragan: So, I think we're continuing to focus on the high unmet need and to present the value proposition that would support sort of a uniform pricing strategy across multiple indications. Okay, that's helpful. And I know you mentioned clearing the 600 MIG dose in Waldenstrom's. How many patients were initiated on the 600 MIG dose? Are those the six patients in that third cohort? Yeah, hi, Steve. This is Diego.

Those that we've seen with whim syndrome. So I think we're continuing to focus on the high unmet need and to present the value proposition that would support sort of a human uniform pricing strategy across multiple indications.

Okay.

That's helpful and I know you mentioned clearing with 600 gig dosing walton's drums.

How many patients were initiated almost 600 gig doses that the six patients in that in that third cohort.

Okay.

Diego Cadevid: Yes, in cohort B, the goal was to enroll six patients and five out of six minimum with no major safety events. And that was accomplished. That's why this morning we announced that the 600 milligram, the top dose, has now been cleared, and all remaining patients in the trial who were at the lower doses are being dose escalated. So we expect, at the end when we report updated results in the second half, everyone who is eligible will be at 600 milligrams for a number of months. Okay, and you'll have five patients on who were initiated at 600MGZ. Yes, the goal was yes.

Yes, Hi, Tim This is diego, yes, the cohort b.

Thank God Westway enrolled six patients.

<unk> six <unk> with no manual safety events.

<unk> accomplished that's why this morning, we announced that the 600 milligram. The top dose has now been cleared now remaining patients seen that pattern.

The lower doses have been dose escalated so we expect.

At the end of <unk>, when we report out data we saw in the second half.

One will you sell as you will be at 600 milligrams for a number of months.

Okay, and you'll have five patients who were initiated at the 600 megahertz.

Yes, the <unk>, yes, okay.

Stephen Willey: Okay. And then, just lastly for Adam, do you have a share count as of year end? Yeah, so it's about 30 million basic shares outstanding. And then we have another 9 million if you include the Class A and Class B warrants.

And then just lastly for Adam do you have the share count as of.

As of year end.

Yes, so it's about 30 million basic shares outstanding.

And then we have another $9 million. If you include the class a and class B warrants.

And then lastly about $1 million of options <unk>, so $40 million that was a good number fully diluted.

Adam Mostafa: And then lastly, about a million options RSU. So 40 million or so is a good number fully diluted. Great. Thanks for taking the question. Thank you. Our next question comes from Marc Frahm with Colin and...

Great. Thanks.

Thanks for taking questions.

Thanks, Steve.

Our next question comes from Marc Frahm, with Cowen and company.

Marc Frahm: Thanks for taking my questions. Paula, with the work you've done on identifying novel mutations, I wonder what your latest thoughts are on how many WIMP patients actually exist in the U.S.? Has this mostly just reinforced your confidence in the numbers you've put out, or are you thinking maybe those numbers need to be increased? Well, I think so. For us, it's always about confidence first.

Hi, Thanks for taking my questions.

Paul with the work you've done on.

Hey, Dan Thank novel mutations I guess, what are your latest thoughts on how many when patients actually exist in the U S. Just mostly just reinforce your confidence in the numbers you put out or are you thinking maybe those numbers need to be increased.

Paula Ragan: And so, of course, these additional variants are increasing our very deep confidence in the 1,000 to 3,700 range that we have presented. Certainly, as we learn more, and we'll look forward to providing some updates this year about the variants that we're identifying through multiple avenues, we will think about revising as we think that's appropriate. But for now, it's really about confidence.

Okay.

I think so for us it's always about confidence first and so of course. These additional variance are increasing our very deep confidence in the 1000 3700 range that we have presented certainly as we learn more and we will look forward to providing some updates even this year about the variance that we're identifying through multiple avenues.

Paula Ragan: And again, you can appreciate that we want to always go up is the strategy of the company. So confidence in that 1,000 to 3,700 is our position today, but certainly there's probabilities that we could increase that in the future. Okay, that's helpful. And then on the SCN update that we're expecting, just give a little more clarity on the number of patients we should expect and the amount of follow-up that they'll likely have. Compared to what we saw back in, [inaudible] Yeah, hi.

We will think about revising as we think thats appropriate but for now it's really about the confidence and again you can appreciate we want to always go up.

The of the company so confidence in that 1000 to 3700 days are positioned today, but certainly there.

Probability of that could increase that in the future.

Okay.

And then on the SDN update that we're expecting.

Yes.

More clarity on the number of patients we should expect the amount of follow up.

So like we've had.

Versus what we saw back in December .

Unknown Executive: We, as you know, we presented data on the first four patients at ASH. We are actively identifying and enrolling patients. So we are prepared to release data on more than four patients. Certainly, the study is up to 25. And we are working with all the sites. There's interest in the study and the conditions of the pandemic have improved. And that's also something that is helping us. Okay, and then maybe one for Adam.

Yes, hi.

We presented data on the first full patient set us we are actively.

Identifying and enrolling patients. So we are prepared to release data on more than four patients. So that's on me.

The study is up to 25, and we are working with all the sites.

There is interest in this study the conditions of the pandemic tap improved and that's also something that is helping us.

Okay. That's helpful and then.

Maybe one for Adam.

Adam Mostafa: The cash guidance... It seems to be kind of tied to the year-end cash balance, but you did do a private placement the other day. Is that actually included in the cash guidance? And if not, how does that impact your guidance around that?

The cash guidance.

It seems to be tied to the yearend cash balance that you did do a private placement the other day.

Does that does that actually included in the in the cash guidance and if not how do.

Does that.

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Your guidance around there and then related to that is can you remind us what the minimum cash covenants are for some of the debt.

Adam Mostafa: And then related to that is, can you remind us what the minimum cash covenants are for some of the debt? Sure. Yeah, thanks, Mark. So our guidance remains into the fourth quarter. That includes the $6 million or so you referenced that we raised since the beginning of the year. It just puts us further into the fourth quarter. On the Hercules side, we have a minimum cash covenant of six months of cash.

Sure Yeah. Thanks, Mark So our guidance remains into the fourth quarter that includes the $6 million or so you referenced that we've raised since the beginning of the year.

Puts us further into the fourth quarter.

On the Hercules side, we have a minimum cash covenant of six months of cash we did recently amended and if we raised $30 million from any source by June 30th that minimum cash covenant becomes a fixed 30 million so more flexibility less than six months of cash currently.

Adam Mostafa: We did recently amend it, and if we raise $30 million from any source by June 30th, that minimum cash covenant becomes a fixed $30 million, so more flexibility, less than six months of cash currently. And that test kicks in on September 1st, as we also pushed that test date out recently. Okay, great. Very helpful.

And that test kicks in on September one.

We also pushed that test data out recently.

Okay, great very helpful. Thank you.

Sure.

Our next question comes from my Young Moms tiny with B Riley Securities.

Marc Frahm: Thank you. Our next question comes from Mayang Mamtani with B. Reilly. Good morning.

Unknown Attendee: Thanks, Dean, for the detailed updates. So, a couple of questions from us. Just on the full WIM study, in terms of how you're thinking about presenting the data, top line, and also the full data set, would you have information on the patient level analysis? And if at all, you're targeting any medical conferences towards the end of the year? And just so I think we heard your question was around how are we how and kind of what are we going to present around the top line data, both in terms of initial top line, and then possibly at a medical conference, just to reiterate that, correct? Yes.

Good morning, Thanks, Dan for the detailed update.

Couple of questions from US just on the core Vin study.

In terms of how youre thinking about presenting the data adult line and also the full data set.

Would you have information on the patient level analysis.

And if the dollar youre targeting any medical conferences towards the end of the year.

My name just I think we heard your question was around how are we how and kind of what are we going to present around the topline data. Both in terms of initial topline and then possibly at a medical conference just to reiterate is that correct.

Yes.

Unknown Executive: Okay, here you go. Yes, so we always aim to present top-line data at medical conferences. So right now, we have not specifically pointed to what conference, but Q4 is when we are tracking. So obviously, we look for the best venue at that time to disseminate the data. We're really looking forward to it.

Okay Diego.

Yes so.

We are always saying, 2% top line data at medical conferences. So.

Right now we have not specifically pointed to what confidence that Q4 is when we are tracking.

So obviously, we would look for the best but any light at that time, so the semi needed data.

We're really looking forward to eat.

Blind data is will be only part of that the study has many other endpoints so through the following months.

Unknown Executive: Top-line data will be only part of that; the study has many other end points. So through the following months and other conferences, we plan to disclose all the other valuable data that we are collecting. Okay, and maybe on that, do you plan to disclose additional baseline characteristics kind of information now that, you know, you have a lot of information on these 31 patients that are enrolled? Would there be some more information on those patients, or should we just wait until the final top line?

Another confidences, we plan to disclose all the other valuable data that we're collecting.

Okay.

Just maybe on that.

Do you plan to disclose this.

No baseline.

This kind of information now that you have a lot of <unk>.

Information on these 71 patients that are enrolling would there be.

Some more information on those patients or should we just wait until the final top line.

Unknown Executive: Yeah, so soon, at an upcoming conference, there will be a poster that will include baseline characteristics, so you will be able to see the type of patients that were enrolled into the trial. So that's coming very soon. It's awesome. And then on the B8-4H missense mutation, the poster you had at the Quad Conference, just about the implications of that, does that help expand prevalence or also identify maybe more severe patients with that lymph phenotype? Could you just clarify that?

Yeah. So soon.

Add on incoming confidence there will be a poster.

And that will include baseline characteristics or you will be able to see there the type of patients where they run into the past so that's coming very soon.

Awesome.

And then on the <unk> MX ones mutation. The poster you had the Quad conference.

Just about the implications of that does that help expand Greg lynds.

So identified maybe more severe patients.

With that then.

Could you just clarify that.

Unknown Executive: So, mind, just to clarify, again, I think this is in reference to the D84H disclosure that we had where we identified a series of patients with that. So, the good news is, I think that, as I think earlier, you know, questions about that increase our confidence. And then does it change our numbers? So, right now, I think we're very squarely in the camp of increasing our confidence in that, that thousand to 3700, you know, even just based on that one mutation alone. However, maybe I'll invite Art to just comment broadly.

84, it sorry, Mike just to clarify again I think this is in reference to the day 84 H.

Disclosure that we had where we identified a series of patients with that so the good news is I think that as I think earlier question does that increase our confidence and then does it change our numbers right now I think we're very squarely in the camp of increasing our confidence into the thousands of 3700, you know even just based on that one mutation.

Alone However, maybe I'll invite our to just comment broadly on some of the additional work that we're doing on additional variance and there'll be more data to come this year art.

Art Tavares: On some of the additional work that we're doing on additional variants, and there'll be more data to come this year. Art?

How are you doing.

So as you know we've been characterizing a number of mutations that we've identified through our own research through the clinical programs through the literature through in detail. The path forward program and then we transfect cells and tried to characterize that perhaps you're nicely. So we've done that with many tens.

Okay.

Well over 50, I'll, just say right now and then we're going to be communicating that data set throughout the year.

Art Tavares: Yes. Hi, bye, Akiko. So, as you know, we've been characterizing a number of mutations that we've identified throughout our own research through the clinical programs, through the literature, through in detail, the path forward program. And then we transfect cells and tried to characterize their path to the city. So, we've done that with many tens are actually well over 50. I'll just say right now, and then we're going to be communicating that data sets throughout the year.

341, why which is coming up at <unk>, we presented as you know last year and then as part of that we look at the number of genomics databases and calculate what I would say is a very conservative number of prevalence and so for that or is it actually allows us to understand the opportunity we work with other people to try to communicate.

The details of the pathogenic findings that were seeing and Thats all part of education community.

Art Tavares: We have the S341Y, which is coming up at CIS, D84H. We presented it as, you know, last year. And then, as part of that, we look at the number of genomics databases and calculate what I would say is a very conservative number of prevalence. And so, for that, it actually allows us to understand the path to ethnicity. We work with other people to try to communicate the details of the pathogenic findings that we're seeing. And that's all part of education.

We anticipate that there are many more patients out there with these various mutations actually are pathogenic. It demonstrates some type of win so thats really about the future and we're happy to disclose a lot of that information as we keep moving forward.

Unknown Executive: The community and we anticipate that there are many more patients out there with these various mutations that actually are pathogenic and demonstrate some phenotype with WIM. So, that's really about the future. And we're happy to disclose a lot of that information as we keep moving forward. Thank you. And then my final question on William Strong's, great to see the 600 mid-dose clearance. Can you just clarify what your target for deepening of responses looks like now that you're at higher doses and exposure is going beyond 12 months for these patients? So just, could you just clarify what sort of MR and VGPR numbers you might be targeting? Yeah, this one. Thanks for the question.

Thank you and then my final question on volumes strong great to see the extended make those clearing.

Gladys why would you target.

For deepening of responses look like now that you had higher dose exposure is going beyond 12 months for these patients.

Gladys.

Gladys outside of MRI with Upi numbers, you might be targeting.

Unknown Executive: So the study was designed as intrapatient dose escalation. Everybody started at 200 milligrams in combination with ibrutinib. Once 200 mg was deemed safe, everybody eligible was those escalated to 400. And then they stay at 400 until the 600 mg dose was deemed safe, which just happened. And now we have a good number of patients already at 600, and another good number that are being escalated to 600. So this will result on a variability of exposure at 600 over time.

Yes, thanks for the question so.

<unk> was the sign of intra patient dose escalation.

Everybody excited at 200 milligrams in combination with Ibrutinib.

Once 200 milligram was deemed safe everybody eligible west dose escalated to 400 and then they stay at 400 to six.

600 milligram dose was deemed safe, which just happened and now we have a good number of patients already have 600.

Another good number that are being escalated to six candidates. So this way we sold on why they are really two of exposure that 600 always tying some patients will be a need for a much longer lives for a shorter time.

Unknown Executive: Some patients will be on it for much longer, others for shorter times, and overall, we believe this is really good news. Combining fibrotinib with this highest tested dose, we believe over time, it gives this possibility of having deeper, more durable, more pronounced clinical responses.

Oh wait only we believe D. C. So really good meals combined combination of Ibrutinib with this highest dose we believe overtime.

<unk> this a possibility of having deeper more durable more pronounced clinical responses. So over the next few months, we will be looking at all this data and we will communicate eating the second half as this data becomes available.

Unknown Executive: So over the next few months, we will be looking at all this data, and we will communicate it in the second half as this data becomes available. Thank you for taking our questions. Ladies and gentlemen, as a reminder, to ask a question, simply press star 1 on your telephone to get in the queue. We do have a question from the line. Edward H.C. Winwright, please. David Bautz, David Bautz, David Bautz, David Bautz. Hey, good morning, everyone. This is Arthur in 4RK.

Thanks, Thank you for taking my question.

All right, ladies and gentlemen, as a reminder to ask a question simply press star one on your telephone to get into queue.

We have a question from the line of our two alright with H C. Wainwright. Please go ahead.

Unknown Attendee: Thanks for taking my question. So, I guess I just want to follow up on patient enrollment for the WaterStone study. So, how many total patients have right now been enrolled in the total study? And how many patients have been dosed at the 600 milligram dose level? Yes, the study calls for the enrollment of 12 to 18 patients. We have not communicated the exact number, but we are in a good position to meet that enrollment goal.

Hey, good morning, everyone and thank you Arthur for RK. Thanks for taking my question.

So I guess I just wanted to follow up on the.

Patient enrollment.

Toward the strong study.

Yes, hi.

How many patients total patient to have right now being.

Relative.

Total.

Study and.

How many patients that has being dosed at four 600 milligram dose level.

Yes, Thanks, Tycho for the enrollment of 12 to 18 patients we have not.

A unique case.

Exact number but we are in a good position to meet that enrollment goal.

Diego Cadevid: And as I said recently, everyone eligible will be at the 600 milligram dose, and we believe that that sample size at that dose will give us the information we need to plan for the next step. Okay, thanks. And maybe a little bit of follow up on that.

As I said recently, everyone eligible will be at the 600 milligram dose and we believe that that sample size said that though when you gave us the information we need to plan for the next step.

Unknown Attendee: Is the newly enrolled patient or folks on both including or naive and refractory patients, or does it have a more concentrated focus on the refractory? So the current protocol allows for enrollment of either frontline or relapsed refractories. There's an effect of the label, like routine if it's approved in the U.S. for a frontline but not in Europe, so it really depends on which site it's being enrolled at. But we, as we communicated at ASH, have been enrolling both types. And we believe combination treatment has the potential to help both types of patients.

Okay. Thanks.

Maybe a little bit of follow up on that.

Is the.

Newly enrolled patients.

Folks on both are including or naive and a refractory patient or.

More concentrated in the refractory patient.

So the current protocol allows for enrollment of either from lines all relapsed refractory.

There is some effect of the label Ibrutinib piece.

Approved in the U S for frontline, but not in Europe , so it really depends on which side each enrolling but we as we communicated at ash, we have been enrolling both types.

Believe the combination treatment has the potential to have both types of patients.

Diego Cadevid: Thank you. Thanks for taking my question. Thank you, and I'm, Thank you. I will turn the call back to Paula Ragan for her final question. Well, thank you again for joining us today. We look forward to seeing many of you at the various upcoming investor conferences and at medical meetings throughout the year. Please, if you have any further questions, don't hesitate to reach out to Glenn, and we hope you enjoy the rest of your day. Thanks so much. And with that, ladies and gentlemen, we conclude our program for today. Thank you for participating, music playing music playing music playing music playing, music playing,

Thanks, Thanks for taking my question.

Thank you and I'm not showing any further questions in the queue I will turn the call back to Paula Ragan for her final remarks.

Well. Thank you again for joining US today, we look forward to seeing seeing many of you at the various upcoming investor conferences and at medical meetings throughout the year. Please if you have any further questions don't hesitate to reach out to Glen and we hope you enjoy the rest of your day. Thanks, so much.

And with that ladies and gentlemen, we conclude our program for today. Thank you for participating.

You may now disconnect.

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