Q3 2021 X4 Pharmaceuticals Inc Earnings Call
Daniel Ferry: I'd now like to turn the call over to Paula Reagan. Okay, Paula?
Paula Ragan: Thanks, Dan, and thank you everyone for joining us on the call this morning, where we plan to discuss our upcoming presence at the Ash December meeting, along with highlights of the recent quarter and our financial results. In doing so, we hope to convey the level of excitement here at X4 as we head into what promises to be a very catalyst-rich period for the company.
Paula Ragan: As detailed in the press release that just went out, we have had all seven of our submitted abstracts accepted for publication at Ash, with four accepted to be presented as posters. This conference will be the largest presence ever for X-4 at a medical meeting and represents the culmination of several years of incredibly hard work and success across our entire organization. We also just announced that we will be hosting an Investor Day on December 16th, just following the Ash meeting, to discuss the data in greater depth and to hear from a number of prominent key opinion leaders who will help put all of these data into context. So please save the date for that X-4 event.
[music].
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.
Dan theory lifestyle advisors. Please begin.
Thank you operator, and good morning, everyone. Thanks for joining us presenting on today's call will be <unk>, Chief Executive Officer, Dr. Paula Ragan.
The Companys Chief Financial Officer, Adam staffer following prepared remarks by each we will open up the call to your questions and we'll be joined by Chief Scientific Officer are Tavares, Chief Medical Officer, Diego cut of it and Chief operating Officer Mary <unk>.
Paula Ragan: The abstract published today on the Ash website contains a very broad array of both clinical and scientific data, data that we believe not only further establishes X-4 as a leader in the CXCR4 space but that also support the broadening scope of the clinical potential of our lead candidate Maverick's A4. As you know, Maverick-Sepore is the only CXR-4 antagonist being developed in an oral once-daily formulation. We are currently conducting three clinical trials of Mavericks 4 across a number of indications. The first is our global, pivotal phase three trial in people with WIM syndrome.
As a reminder, on today's call the company will be making forward looking statements regarding regulatory and product development plans as.
As well as research activities.
These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.
A description of these risks can be found in <unk>. Most recent filings with the SEC I'd now like to turn the call over to Paula Ragan Paula.
Thanks, Dan and thank you everyone for joining us on the call. This morning.
And to discuss our upcoming presence at the Ash December meeting along with highlights of the recent quarter and our financial results.
Doing so we hope to convey the level of excitement here for as we head into what promises to be a very catalyst rich period for the company.
As we detailed in the press release that just went out we have had all seven of our submitted abstracts accepted for publication at Ash with four accepted to be presented as posters.
Paula Ragan: Importantly, we achieved a major milestone in early October, completing enrollment in the Phase 3 clinical trial. 31 adult and pediatric patients have been enrolled in the trial, which was originally designed to enroll 18 to 28 patients with WIM syndrome. Topline data from this trial are anticipated in the fourth quarter of 2022. WIM is a rare inherited primary immunodeficiency caused by a variety of mutations in the CXCR4 receptor gene that cause immune cell dysregulation. This digitigulation inhibits the proper maturation process for the entire range of white blood cells and causes them to get trapped in the bone marrow, preventing healthy trafficking and systemic circulation.
This conference will be the largest presence ever for export at a medical meeting and represents the culmination of several years of incredibly hard work and success across our entire organization.
We also just announced that we will be hosting an investor day on December 16th just following the ash meeting to discuss the data and greater depth and to hear from a number of prominent key opinion leaders, who will help put all of these data into context.
Please save the date for that export event.
The abstract published today on the Ash website contain a very broad array of both clinical and scientific data.
That we believe not only further establishes <unk> as a leader in the <unk> space.
That also support the broadening scope of the clinical potential of our lead candidate Maverick before as you know Maverick support is the only <unk> four antagonist being developed and an oral once daily formulation.
We're currently conducting three clinical trials of maverick's four across a number of indications.
The first is our global pivotal phase III trial in people with whim syndrome.
Importantly, we achieved a major milestone in early October completing enrollment in the phase III clinical trial.
Paula Ragan: This results in lifelong challenges to the health and well-being of WIM patients, including severe, recurrent, and sometimes life-threatening infections, loss of lung function and hearing, and significantly increased risk for HPD-associated cancers. By correcting this CXR4 dysfunction, Mavericks 4 has been shown to not only increase the levels of circulating neutrophils, monocytes, and lymphocytes in WIM patients but also to reduce the number and severity of annual infections and to reduce warts caused by unchecked HPV infections.
<unk> 31, adult and pediatric patients had been enrolled in the trial, which was originally designed to enroll 18 to 28 patients with whim syndrome top line data from this trial are anticipated in the fourth quarter of 2022.
When is a rare inherited primary immunodeficiency caused by a variety of mutations in the <unk> four receptor gene that causes immune cell dysregulation.
With this regulation inhibits the proper maturation process for the entire range of white blood cells and causes them to get trapped in the bone marrow, preventing healthy trafficking and systemic circulation.
This results in lifelong challenges to the health and wellbeing of when patients, including severe recurrent and sometimes life threatening infections lots of lung function and hearing and significantly increased risk to HPV associated cancers.
By correcting the <unk> dysfunction Maverick for has been shown to not only increase the levels of circulating neutrophils monocytes and lymphocytes and when patients, but also to reduce the number and severity of annual infections and to reduce work caused by unchecked HPV infections.
Paula Ragan: One of our abstracts accepted for poster presentation at Ash further highlights similarly positive data from our ongoing phase two open-label extension trial in patients with WIMM and includes patient interviews that reveal that all four of the continuing study participants experience good tolerability and beneficial treatment effects when dosed with Mavericks before a long term. Also relating to WIM, several abstracts published this morning focus on WIM-causing CXR4 mutation variants and on the U.S. prevalence of the disease. As a quick background, there have been 16 whim-causing CXR-4 receptor mutations identified to date, all of which have been located in the internal tail, known as the C terminus of the receptor.
One of our abstracts accepted for poster presentation at Ash further highlight similarly positive data from our ongoing phase II open label extension trial in patients with a whim.
It includes patient interviews that reveal that all for the continuing study participants experienced good tolerability and beneficial treatment effects when dosed with Maverick before long term.
Also relating to win several of the abstract published this morning focus on wind, causing <unk> mutation variance and on the U S prevalence of the disease.
As quick background, there have been 16 wind, causing <unk> four receptor mutations identified to date.
All of which have been located any internal kale known as the C terminus of the receptor.
Paula Ragan: Driven by our patient identification efforts, in DIPATE, collaboration, and clinical trial screening efforts, we have identified a host of patients with both these known CXCR4 variants and also novel CXR4 mutations. As a result, we have been able to better learn about the disease spectrum of WIM, both clinically and genetically, and have established research that enables the correlation of a patient's WIM symptoms with increased TXCR This is referred to as genotype-phenotype correlation.
Driven by our patient identification efforts MVP collaboration and clinical trial screening efforts, we have identified a host of patients with both these known <unk> variance and also novel <unk> mutations.
As a result, we have been able to better learn about the disease spectrum of when both clinically and genetically and have established research that enables the correlation of a patient when symptoms with increased <unk> signaling caused by genetic mutations.
This is referred to as genotype phenotype correlation.
Paula Ragan: In the abstract describing a novel variant, we specifically published our first discovery resulting from these efforts, which describes a novel mis-sense mutation called D84H discovered in collaboration with treating physicians and X-4 scientists. The D-84H mutation is the first mutation identified outside of the C terminus of the CXCR4 receptor, and we have shown through our internal research that this mutation causes gain of function signaling correlating with the disease phenotype of WM patients. To look further into this newly identified mutation, we also analyzed multiple broad population genomic databases, which helped us determine that the allele frequency of the D84H mutation is very high in the generalized population.
And the abstract describing a novel variance, we specifically publish on our first discovery, resulting from these efforts, which describe a novel Ms sense mutation called D 84, H discovered in collaboration with treating physicians and X where scientists.
The day 84, <unk> mutation is the first mutation identified outside of the determinants of the <unk> four receptor.
And we have shown through our internal research that desk mutation causes gain of function signaling correlating with the disease phenotype when patients.
To look further into this newly identified mutation. We also analyze multiple broad population genomic databases.
Which helped us determine that the allele frequency of the day 84, H mutation is very high and the generalized population.
Paula Ragan: Using the current U.S. population and a conservative estimate of 5% to 10% of individuals who go on to develop the disease symptoms, also known as penetrance, these data support that there are at least 1,250 to 2,500 WAM patients in the U.S. resulting from the D84H mutation alone. They have found multiple D84H patients from different families across the world in the brief time since the discovery, which further validates the finding. We plan further patient identification efforts to deepen the validation of the D84H prevalence estimate and to explore similarly identified CXR4 for a variance that could impact prevalence estimates in 2022 and beyond.
Using the current U S population and a conservative estimate of 5% to 10% of individuals who go on to develop the disease symptoms also known as penetrates.
These data support that there at least.
<unk> 1250 to 2500 when patients in the U S, resulting from the day 84 H mutation alone.
We have found multiple data for each patients from different families across the world in the brief time since the discovery, which further validates we're finding we plan for further patient identification efforts to deepen the validation of the data for each prevalence estimate and to explore similarly identified CX here, where variance that could in.
Pac prevalence estimates in 2022 and beyond.
Paula Ragan: Together, this patient identification and bench to bedside research, along with our prior market research and our artificial intelligence research published in these abstracts, continues to reaffirm our belief that WIM is a significantly under-recognized and underdiagnosed condition, and that the true population may be much larger than is currently reported.
Together this patient identification and bench to bedside research along with our prior market research and our artificial intelligence research published in these ash abstract.
To reaffirm our belief that <unk> is a significantly under recognized and under diagnosed condition and that the true population may be much larger than is currently reported.
Paula Ragan: We plan to go into more detail regarding our ongoing patient finding activities at our investor event in December, but needless to say, we are very encouraged by the results that our studies are elucidating, building support, and awareness among the rare disease physician community as we continue to ramp up our pre-commercial activities in advance of our expected phase three top line data, which as I mentioned are anticipated in the fourth quarter of 2022. Let's now shift to updates on our ongoing clinical trial and chronic neutropenia, which is an indication that nicely leverages our successful experiences with WIM syndrome, our broader trial experiences, and input from our clinical community.
We plan to go into more detail regarding our ongoing patient finding activities at our investor event in December but needless to say we are very encouraged by the results that our studies are elucidating building support and awareness to the rare disease physician community as we continue to ramp up our pre commercial activities.
In advance of our expected phase III top line data.
As I mentioned are anticipated in the fourth quarter of 2022.
Let's now shift to updates on our ongoing clinical trial in chronic neutropenia, which is an indication that nicely leverages, our successful experiences with whim syndrome or broader trial experiences and input from our clinical communities.
Paula Ragan: We believe the treatment opportunity for Mavericks in chronic neutropenia is quickly becoming an additional key value driver for X4 based on new long-term data. Specifically, one of the Ash Abstracts accepted for post-re presentation demonstrates that Mavericks alone or in combination with other therapies, acutely and chronically, increases total peripheral white blood cell counts 1.5 to three-times baseline across a number of different diseases in both the presence and absence of the CXCR4 mutations.
We believe the treatment opportunity for Maverick sport and chronic neutropenia is quickly becoming an additional key value driver for <unk> based on new long term data.
Specifically one of the Ash abstracts accepted for poster presentation demonstrates that maverick for alone or in combination with other therapies acutely and chronically increases total peripheral white blood cell counts one five to three times baseline across a number of different diseases and both the present.
And absence of the <unk> mutations.
Paula Ragan: This suggests that Maverick's Port could uniquely provide benefit to patients with broad chronic neutropenia conditions. And given its profile as an oral once daily administration, we believe Mavericks, the Forest, is positioned to potentially become standard of care in a treatment landscape only addressed currently by injectable therapies.
This suggests that Maverick <unk> can uniquely provide benefit to patients with broad chronic neutropenia condition.
<unk> given its profile as an oral once daily administration, we believe maverick before us positioned to potentially become standard of care in a treatment landscape only address currently by injectable therapies.
Paula Ragan: Based on the extensive and long-term data we presented in the abstract and based on input from our clinical advisors, we have amended our ongoing Phase 1B Nutropenia trial to include a broader range of neutropenia conditions, including patients with severe and moderate neutropenia. We are now also enrolling all patients, whether or not they are being treated with the standard of care, which is granulocyte colony stimulating factor or GCSF, and whether or not their neutropenia is caused by a genetic mutation.
Based on the extensive and long term data we presented in the abstract and based on input from our clinical advisors. We have amended our ongoing phase one being neutropenia trial to include a broader range of neutropenia conditions, including patients with severe and moderate neutropenia.
We are now also enrolling all patients whether or not they're being treated with the standard of care, which is granulocyte colony stimulating factor or G. CSF.
And whether or not theyre neutropenia caused by a genetic mutation.
The trial is assessing the safety and Tolerability of two weeks of dosing in cohort, a and a single dose of Maverick sport in cohort b and measuring the effect of doses on patient neutrophil counts along with other white blood cell type.
Paula Ragan: The trial is assessing the safety and tolerability of two weeks of dosing in cohort A and a single dose of Mavericks in cohort B and measuring the effect of doses on patient Nutriphil counts along with other white blood salt types. We've also modified the number of patients to be enrolled to 25, a number we believe will be sufficient to complete the goals of the trial. Our third ongoing trial with Mavericks 4 is designed to demonstrate safety dose and elucidate proof of concept in a rare B-cell lymphoma called Walden Troms macroglobulinemia.
We've also modified the number of patients to be enrolled to 'twenty five a number we believe will be sufficient to complete the goals of the trial.
Our third ongoing trial with Mavericks four is designed to demonstrate safety dose and elucidate proof of concept in a rare b cell lymphoma called Walden trumps macro globular anemia.
While greater than 90% of patients with Walden trends have acquired mutations in what's called the <unk> gene.
Subset about 30% to 40% also have acquired mutations in <unk>.
A significant clinical unmet need in these double mutation patients where the presence of the <unk> mutation.
When patients, causing white blood cells, including their abnormal diesel to be stuck in the bone marrow.
Paula Ragan: While greater than 90% of patients with Waldenstrom's have acquired mutations in what's called the MYD8 gene, a subset, about 30 to 40% also have acquired mutations in CXR4. There is a significant clinical unmet need in these double mutation patients where the presence of the CXCR4 mutation, as with WIM patients, causes white blood cells, including their abnormal B cells, to be stuck in the bone marrow. This sequestration of cells can prevent patients from responding well to standard of care BTK inhibitor treatment.
This sequestration itself can prevent patients from responding well to the standard of care PTK inhibitor treatment.
Manifests as delayed response inferior depth of response <unk> shorter progression free survival.
Our phase one trial is evaluating the safety and Tolerability of Maverick for in frontline and treatment refractory Walton from patients at doses of 200 406 hundred milligrams in combination with Ibrutinib.
Both agents are delivered orally once daily in patients with confirmed <unk> and <unk> mutations. The study is also measuring change from baseline and IGN in hemoglobin pharmacokinetics and Pharmacodynamic markers, which include measurements of peripheral white blood cell counts in addition to <unk>.
<unk> clinical response rates.
Paula Ragan: This can manifest as delayed response, inferior depth of response, and or shorter progression-free survival. Our Phase 1B trial is evaluating the safety and tolerability of Mavericks for in-frontline and treatment-refractory Waldenstrom patients at distances of 200, 400, and 600 milligrams in combination with brutinib. Both agents are delivered orally once daily in patients with confirmed NYDA-8 and CXCR4 mutations.
As you May recall this past June we presented the first data from this initial trial and an E poster at the 2021 European Hematology Association meeting.
In the poster and on our Investor call that day, we presented details during the first eight patients enrolled in the study.
Those data were very encouraging with Maverick <unk>, plus ibrutinib, demonstrating good tolerability and biomarker data, suggesting best in class potential for this combination treatments.
The cutoff date for the Ash abstract filing was so close to this event and data announcements. The ash abstract contains a fairly modest amount of incremental data beyond what we presented at Aha.
Paula Ragan: The study is also measuring change from baseline in IGM and hemoglobin, pharmacokinetics, and pharmacodynamic markers, which include measurements of peripheral white blood cell counts in addition to measuring clinical response rate. As you may recall, this past June, we presented the first data from this initial trial in an e-poster at the 2021 European Hematology Association meeting. In the poster and on our investor call that day, we presented details about the first eight patients enrolled in the study.
As of the abstract cutoff date of June 15th 2021. The overall response rate, which is minor response or better than the eight patients evaluated at the time was 100%.
Four of the eight patients achieving a major response, which is greater than a 50% reduction in serum IGN and one of the eight patients achieving a very good partial response, which is greater than a 90% reduction in serum IGN.
We do plan to have additional data at the ash poster with a data cutoff of mid October and we look forward to a deeper review of overall response rates at the meeting and at our Investor Day in December we remain very encouraged by our <unk> program potential as we continue to see encouraging signals emerging across patient groups.
Within the phase one b trial.
Paula Ragan: Those data were very encouraging, with Mavericks for a plusabrutinib demonstrating good tolerability and biomarker data suggesting best-in-class potential for this combination treatment. Because the cutoff date for the Ash Abstract filing was so close to this event and data announcements, the Aftract contains a fairly modest amount of incremental data beyond what we presented at EHA. As of the abstract cutoff date of June 15th, 2021, the overall response rate, which is minor response or better, and the eight patients evaluated at the time was 100%, was four of the eight patients achieving a major response, which is greater than a 50% reduction in CRM IGM, and one of the eight patients achieving a very good partial response, which is greater than a 90% reduction in CRM IGM.
So as you can see we are very excited about the data we've revealed so far and about the expanding potential of maverick's floor, and we're really looking forward to our presentations at Ash and tour our investor event, just following the meeting.
We will be providing more details about the event in the coming weeks, but we currently expect it to be a two hour virtual meeting on the morning of December 16th with participation from our expert clinical advisors. So please mark your calendars.
With that update I'll now turn it over to Adam to discuss our results for the quarter before we open up the call for questions Adam.
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 results for the third quarter ended September 32021.
Research and development expenses were $13 2 million for the third quarter of 2021.
As compared to $11 4 million for the comparable period in 2020.
General and administrative expenses were $5 9 million for the third quarter of 2021.
As compared to $5 6 million for the comparable period in 2020.
And we reported a net loss of $22 million for the third quarter of 2021 as compared to a net loss of $17 $4 million in the third quarter of 2020.
Note that net losses include $1 5 million and two.
$2 2 million.
Certain non cash expenses for the quarters ended September 32021, and 2020, respectively.
Paula Ragan: We do plan to have additional data at the Ash poster with a data cutoff of mid-October, and we look forward to a deeper reveal of overall response rates at the meeting and at our Investor Day in December. We remain very encouraged by our Waldstrom program potential as we continue to see encouraging signals merging across patient groups within the Phase 1B trial. So, as you can see, we are very excited about the data we've revealed so far and about the expanding potential of Maverick's score.
We had $77 7 million in cash cash equivalents and restricted cash as of September 32021.
We continue to expect that these funds will support our operations into the fourth quarter of 2022.
We did make some personnel announcements towards the end of the third quarter.
We announced the appointment of <unk>.
<unk> was the quicker to the company's board of directors.
The hiring Carolyn park to the newly created position of Vice President U S commercial.
These appointments significantly strengthen our depth and breadth of commercial leadership experience and expertise in strategic marketing rare disease therapeutics.
In September we announced the promotion of Dr. Mary <unk> to the newly created position of Chief operating officer.
Reflecting our longstanding contributions to the company and the advancement of an average four into global late stage clinical development.
Paula Ragan: And we're really looking forward to our presentations at Ash and to our investor event just following the meeting. We'll be providing more details about the event in the coming weeks, but we currently expect it to be a two-hour virtual meeting on the morning of December 16th with participation from our expert clinical advisors. So, please mark your calendars. With that update, I'll now turn it over to Adam to discuss our results for the quarter before we open up the call for questions. Adam?
Mary has served as our senior Vice President and previously Vice President of technical operations and quality. In addition to Vice President of program and Alliance management.
Joining the company in 2017.
We will now open up the call for your questions operator.
And thank you.
As a reminder to ask a question you will need to press star one on your telephone.
Draw your question press the balance sheet.
Please standby, we compile the Q&A roster and once again that is star one if you'd like to ask a question.
Next question comes from Dave.
Dave Buck Java from Roth capital.
Good morning, and thanks for taking my questions. Congrats on the update and looking forward to the data at Ash and Investor call. I think I just have one general question here and this just about the commercial look I really like.
Adam S. Mostafa: Thanks, Paula, and thanks to all of you on the call today. As presented in our press release this morning, I will summarize our financial results for the third quarter ended September 30th, 2021. Research and Development expenses were $13.2 million for the third quarter of 2021, as compared to $11.4 million for the comparable period in 2020. General and administrative expenses were $5.9 million for the third quarter of 2021, as compared to $5.6 million for the comparable period in 2020.
Youre doing at <unk>.
Looking at expanded market opportunities. We saw you do that the win and now you are looking at SDN and kind of expanding that opportunity can you just comment a little bit on how.
How youre thinking about the execution on that front and more broadly and then as it relates to <unk>, specifically just wanted to get a sense of where you think you are in terms of finding.
The ideal OID.
The two <unk>.
Remember when patients is this a process that you expect to continue to occur even after you launched a program to kind of find additional patients that may benefit from this therapy and also nice to see that you did bring on a VP of commercial Michigan heads at.
The opportunity to really focus on the commercial side of things.
Yes.
Adam S. Mostafa: And we reported a net loss of $20.2 million for the third quarter of 2021 as compared to a net loss of $17.4 million in the third quarter of 2020. Note that net losses include $1.5 million and $2.2 million of certain non-cash expenses for the quarters ended September 30, 2021, and 2020, respectively. We had $77.7 million in cash, cash equivalence, and restricted cash as of September 30, 2021.
Hi, Thanks, so much for the question I'll try to.
Address the components I think.
For people, who understand the history of rare diseases.
Well well established story when it comes.
When a product, especially in innovative products, where theres no treatments first start the number of patients identifies grows exponentially.
Do you think Genzyme as an example way back when the first product in <unk> disease I think at the time. They are about 1000 patients expected to be prevalent in the world and today, we know theres over 15000 based on registry data.
So it really is about education awareness and whim syndrome growing into chronic neutropenia is going to be that story as far as we believe.
When we're learning more about the genetics as you heard finding us unique.
Operator: We continue to expect that these funds will support our operations into the fourth quarter of 2022. We did make some personnel announcements towards the end of the third quarter. We recently announced the appointment of Francoz de Crecourt to the company's board of directors and the hiring of Carolyn Park to the newly created position of vice president, U.S. commercial. These appointments significantly strengthen our depth and breadth of commercial leadership experience and expertise in the strategic marketing of rare disease therapeutics.
Variance based on patients that are already known today is really indicative of our our early understanding of the disease and how it presenting clinically and genetically.
This is a huge step forward for the company in terms of really having profound conviction and our current estimates which will grow over time.
Hope that the story that we've shared about Genzyme and then I think when patients are type of chronic neutropenia, we're learning more and more of that chronic neutropenia as a broader umbrella regardless of genetic foundation is a high unmet need patients today are treated with injectable dcfs multiple times, a day or week.
Inadequate treatment and we can completely revolutionize the therapeutic landscape with an oral once daily. So there is a lot to grow here, where at the start of our commercial journey and in great shape based on some of the data we've just released at Ash.
Thanks, Paul.
Yes.
And thank you.
Operator: In September, we announced the promotion of Dr. Mary DiBiase to the newly created position of chief operating officer, reflecting her longstanding contributions to the company and the advancement of maverixifor into global late-stage clinical development. Mary has served as our senior vice president and previously vice president of technical operations and quality, in addition to vice president of program and alliance management since joining the company in 2017. We'll now open up the call for your questions. Operator.
And our next question comes from Leland <unk> from Oppenheimer. Your line is now open.
Hey, good morning, Paula. Thank you for the update congrats on all the guys. So looking forward to hearing more.
At the meeting.
Question for me kind of touching on.
Prior one I mean, it seems like as we're learning more and more about NAV and it's.
The data that we're seeing in various clinical settings. It seems like there may be no limits in terms of the ability of the content to be useful in a variety of conditions.
Neutropenia.
Limitations on abilities avoid tools to get out of the bone marrow.
As we look forward to your expansion in the clinic and <unk> could you maybe relate to us just.
The expanded scope of the trial and they relate to in terms of the population.
Trial.
Patients in the trial would have corresponded to in terms of let's say the U S population.
Neutropenia. Thank you.
Sure. Thanks, Leland so chronic neutropenia as a marketplace is not well understood, but we can certainly share what we know today and we've been modifying our trial to begin to address this so severe chronic neutropenia is treated as I mentioned with gcs fast and we feel pretty confident today, there's at least 2000 patients.
Operator: And thank you. As a reminder, to ask a question, you'll need to press Star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster, and once again, that is Star 1, if you'd like to ask a question.
On regular G CSF dosing further neutropenia.
That is likely profound underrepresentation of the patients that need it because of the challenges of both G. CSF and the limitations of a label. So we think thats. The beachhead, we think the broader chronic therapy.
Ziva Jala: Good morning. Thanks for taking my questions. Congratulations on the updates and looking forward to the data at Ash and the follow-up investor call. I think I just have one general question here, and it's just about the commercial outlook. I really like what you're doing regarding, you know, looking at expanded market opportunities. We saw you do that for WIM, and now you're looking at SCN and kind of expanding that opportunity. Can you just comment a little bit on, you know, how you're thinking about the execution on that front more broadly?
Larger than that we do have ongoing market research, there and we'll be able to present some of that in 2022, but certainly we think.
There's a lot of unmet need unfortunately.
These patients are not treated well with us and only have a single option. So an oral once daily again could dramatically alter the treatment landscape and market potential for these patients who are somewhat forgotten.
Alright, great look forward to hearing further next month. Thank you.
Thank you.
Thank you.
And our next question comes from <unk>.
For him.
<unk> Company. Your line is now open.
Hi, Thanks for taking my questions and congrats on all the updates.
In your comments you mentioned triangulate.
Triangulating the prevalence of whim patients with the duties for each mutation that you've identified.
Ziva Jala: And then as it relates to WIM specifically, I just wanted to get a sense of where you think you are in terms of finding the ideal or the true number of WIM patients. And is this a process that you expect to continue to occur even after you launch a program to kind of find additional patients that may benefit from the therapy? And also, nice to see that you did bring on a VP of commercial. We can hint at, you know, the opportunity to really focus on the commercial side of the name. Hi Zegba, thanks so much for the questions.
Have you had a chance beyond the case study to kind of go look at some more medical records to kind of.
Inform that 5% to 10% penetrance number that you were putting out there or maybe can you kind of talk about.
The broader context of penetrance just too.
That's an appropriately conservative number obviously the headlines about attendance.
Hi.
Yes.
Yes. This is the hardest.
Sort of assumption for any any new disease area to make as youre going from genetics genotype phenotype.
We have looked at a broad range of.
Other rare diseases, but you can appreciate this is very much I think.
Every every gene is a snowflake story, where there are unique profiles two mutations.
Paula Ragan: Hi Zegba, thanks so much for the question. I'll try to, you know, address those components. You know, I think, for people who understand the history of rare diseases, it's a well-established story of when a product, especially an innovative product where there are no treatments, first starts, the number of patients identified grows exponentially. Just using enzyme as an example, way back when the first product in Gauchet's disease, I think at the time, there were about 1,000 patients expected to be prevalent in the world. And today, we know there's over 15,000 based on registry data.
Thank our our approach here was really being conservative with the 5% to 10%.
You've seen number is actually quite north of that in terms of conversions from.
Genotype or phenotype, but we want to be.
I think.
Appropriately.
Understanding the true prevalence until we start building on it and I think today, we feel very good about what we're seeing with both our patients that we're identifying.
Around that number so it's a tricky one mark thanks for highlighting it I think that's where we're starting today.
Okay. That's helpful. Thanks, and then just walking through.
Yes, absolutely huge.
Huge.
Update in terms of data cutoff for the abstract versus last presentation, but this is the first time that you've included some response data.
IGN levels.
Can you just remind us.
There's some flexibility in the trial as to when patients who require scans for their response assessment when those things happen.
Paula Ragan: So it really is about education and awareness, and WIM syndrome growing into chronic uterpenia is going to be that story, as far as we believe. When we're learning more about the genetics, as you heard, finding this unique variance based on patients that are already known today is really indicative of our early understanding of the disease and how it's presenting clinically and genetically. This is a huge thing.
And can you put in context. The response data that's in there when those scans were taken how many patients actually needed scans for response assessment.
When this happened and then maybe into the broader context of the time course of response seen with I, Brian Hi, Brito monotherapy.
Yes, so I'll ask you to take that I mean big picture Mark at the end of the day, it's sort of about the kinetics of response, I think thats, what youre, saying.
Again, I'll turn it over to deal Diego to provide some more context about our data.
Yes, Thank you Paul on Mark.
Paula Ragan: set forward for the company in terms of really having a profound conviction in our current estimates, which will grow over time, just as I hope the story that we've shared about genzyme. And then I think when patients are a type of chronic neutropenia, we're learning more and more that chronic uterpenia as a broader umbrella, regardless of genetic foundation, is a high-end met need. Patients today are treated with injectable GCSF multiple times a day or week.
So the.
The protocol originally was.
Designed to assess the response starting at six months and then every six months.
In part because Youll have two Hollywood HCP scan, which you see in there.
<unk>.
One marrow biopsies, we have amended the protocol to make that now more frequent every three months.
I would say this update mostly reflects the six months' data, which is sort of the first look into a clinical response.
Recent studies.
<unk>.
Waste, but we felt that it was important to try to get more frequent us as I mentioned thats why we amended.
Okay. That's helpful.
Thank you.
And our next question comes from Stephen Willey from Stifel. Your line is now open.
Paula Ragan: It's an inadequate treatment, and we could completely revolutionize the therapeutic landscape with an oral once daily. So there's a lot to grow here. We're at the start of our commercial journey and in great shape based on some of the data we've just released at Ash.
Hey, good morning, Thanks for taking the questions.
Maybe just following up on Walton's drums.
Understanding that.
Abstract cut is largely representative of what we saw.
But can you speak a little bit to maybe just where patients are in terms of dose escalation in this trial.
Leland Grischel: And thank you. And our next question comes from Leland Grischel from Oppenheimer. Your line is not open.
Specifically with respect to the 600 mid dose and I know that there was an attention to initiate dosing maybe in cohort C 600, migs without the step up can you maybe just speak to kind of where you are.
Leland Grischel: Hey, good morning, Paula. Thank you for the update. Congratulations on all the Ash acceptances.
On the on the dose escalation side.
Sure Diego, we'd like to take that.
Paula Ragan: Looking forward to hearing more at the meeting. Question for me, kind of touching on from the prior one. I mean, as we're learning more and more about MAV and the data that we're seeing in various clinical settings, it seems like, you know, there may be no limits in terms of the ability of the content to be useful in a variety of conditions with, you know, neutropenia and with, you know, limitations on the ability of white cells to get out of the bone marrow.
Yes, sure Steven Yes. So we we have previously communicated of course that we have clear the 200 milligram dose and the 400 milligram dose.
We are already dosing at 600 milligram.
Make much progress.
We plan to report some of that data both in the poster Thats. What you have seen the Investor day. So that's a focus of us to complete that enrollment on just to remind you once once.
600 milligram dose two years in cohort b.
And then everybody else can be escalated to 600, including dosing cohort.
All of those enrolling cohort C.
Okay.
And then just on I guess, the chronic neutropenia or severe congenital neutropenia.
I know these patients don't have CX here for mutations.
But I think the intention of this program was to try to maybe quarterly.
Paula Ragan: As we look forward to your expansion in the clinical neutropenia setting, could you maybe relate to us just what the expanded scope of the trial may relate to in terms of the population? that the trial types of patients in the trial would have corresponded to in terms of, you know, let's say the U.S. population with neutropenia. Thank you.
Responses with some kind of genetic signature and just wondering.
How far along into that interrogation of the correlation will you be.
Time of Ash, and I guess, how much more work do you need to do in order to be able to maybe refine that patient population for responders.
Yes, so I'll make one comment and then I'm going to invite <unk> to talk a little bit more about mechanism because I think it's really indicative of market potential, but we certainly have always been trying to help patients and physicians et cetera understand the genetic drivers of their disease.
As we've just released in our Ash abstracts, we have seen the benefit of Maverick before broadly regardless of mutation status, creating even multiple fold increases in white blood cells, including neutrophil lymphocyte. So there is a huge.
Paula Ragan: Sure, thanks, Leeland. So chronic neutropenia as a marketplace is not well understood, but we can certainly share what we know today, and we've been modifying our trial to begin to address this. So severe chronic neutropenia is treated, as I mentioned, with GCSF, and we feel pretty confident today that there are at least 2,000 patients on regular GCSF dosing for their neutropenias. But that is likely a profound underrepresentation of the patients that need it because of the challenges of both GCSF and the limitations of the label.
Swath of patients that have.
The low neutrophil counts on the lymphocyte counts that this drug could address.
Mechanistically it makes a lot of sense.
I'll end by art and talk a little bit about the mechanism of gcs up with the standard of care in how Maverick really nicely synergizes and could potentially supplement or eventually replace that so art could you chime in.
Sure. Thank you Paul and ICT.
So when we first got started with us yet we actually understood. This.
Different or collection of different mutations did not really include <unk> year. Four. So the question was exactly yours is whether or not that works for could have any kind of benefit.
It would be connected ultimately to <unk> your four up regulation.
Paula Ragan: So we think that's the beachhead. We think the broader chronic problem is larger than that. We do have ongoing market research there, and we'll be able to present some of that in 2022, but certainly, we think there's a lot of unmet need. These patients are not treated well and only have a single option, so an oral once daily, again, could dramatically alter the treatment landscape and market potential for these patients who are somewhat forgotten. Yes,
So as we started to go through and look for mutations that are known that's actually do trigger some kind of metric.
Thank you Jenna and severe congenital neutropenia requirements in Japan, what we find is that so many of them have up regulated CX for so for us that seems to be the premise of the mechanism.
When you have the top regulated CX four which is.
Underlying principle behind a lot of chronic <unk>.
<unk> four would be essentially blocking the adhesion and then you can have a benefit so that's the underlying mechanism and it seems to correlate well with G. CSF administration. So G. CSF as you know Downregulates <unk> for access and that gives you an increase in nutritionals.
And so <unk> four and <unk>.
<unk> is actually part of that mechanism.
It very much aligns with the approach that we're trying to do and we do expect that we're going to have a benefit there and the number of patients that have nothing to do with <unk> mutation.
Paula Ragan: All right, great. Look forward to hearing from you for the next month.
Okay very interesting.
Good questions.
Operator: Thank you. And our next question comes from Mark Fram, from Cowan & Company. Your line is now open.
Thank you.
And our next question comes from MS <unk>.
From B Riley securely.
Your line is now open.
Mark Baldry: Thanks for taking my questions and giving me some updates. Paul, in your comments, you mentioned kind of triangulating the prevalence of limb patients with the D84H mutation that you've identified. I guess, have you had a chance beyond the case study to kind of look at some more medical records to kind of inform that 5 to 10% penetrance number that you were putting out there? Or maybe, you know, can you kind of talk about the broader context of penetration and just explain why that's an appropriately conservative number? Obviously, as a headline, 5 to 10 doesn't seem very high.
Hi, Good morning. This is sahil on for Mike Thanks for taking our questions.
All of them been answered so maybe just a few quick ones in terms of the structure of the data release, how do you anticipate disclosing from me.
SDN and our broader neutropenia program as well as the topline data release from from the wind program is that going to look similar to the phase II and then maybe more of the commercial side could you just talk to kind of how there might be an overlap between the commercial prep for web future neutropenia indications any synergies that you guys are seeing on that end.
Thank you.
Sure. So I think I heard sort of three or four elements of the question so around around the <unk> data.
We will be presenting that data in the context of.
Some of the white blood cell and chronic administration of Maverick before Dave that we've garnered over several trials. So that will be included in our poster and we will share more insights in our investor day on the 16th.
In terms of I think the whim phase III data that certainly top line data expected in about a year.
Paula Ragan: Yeah, now this is the hardest sort of assumption for any new disease area to make as you're going from genetics, you know, genotype to phenotype. So we have looked at a broad range of other rare diseases, but you can appreciate this is very much, I think, you know, every gene is a snowflake story where there are unique profiles for mutations. So I think our approach here was really being conservative with the 5% to 10%.
The primary endpoint as a reminder to everyone at the time of that threshold for neutrophil counts and we had a 600% increase in the phase III. So that that will be kind of the unveil will be in a year from now when the trial completed and then how we're thinking in totality about building the market.
Adjusting the market unmet need around chronic neutropenia is including when we see when is the landmark study to begin to build on our highly targeted population of which you heard is growing from a genetics and phenotype perspective, and then layering on this additional pay.
Paula Ragan: We've seen numbers actually quite north of that in terms of conversions from genotype to phenotype, but we want to be, you know, I think appropriately, um, understanding the true prevalence until we start building on it. And I think today we feel very good about what we're seeing with both our patients that we're identifying around that number. So it's a tricky one, Mark. Thanks for highlighting it. I think that's where we're starting today.
Patient population thats, not necessarily genetically linked but mechanistically linked as we know through through the benefits and CCF Beth.
Again, particularly effective.
<unk> injectable product.
Times multiple times a day for some of these patients.
And we think we can just revolutionize that entire field with an oral once daily starting with whim, and then expanding to the neutropenia beyond it so.
The market.
Footprint commercially or they are treated by the same doctor that's very nicely leverage from an infrastructure perspective and from a patient community perspective, we're learning across all types of neutropenia, So theres, a tremendous amount of connectivity and leverage across that key touch points that we need to be to be long term successful of the court.
Paula Ragan: Okay, that's helpful, thanks. And then just on Waldenstrom's, yeah, I would say it's not a huge update in terms of data cutoff for the abstract versus the last presentation, but this is the first time that you've included some response data, not just the IGM levels. Can you just kind of remind us that I think there's some flexibility in the trial as to when patients who require scans for their response assessment when those scans happen?
As an organization.
Sure.
Awesome, that's really helpful. Congrats on the progress.
Thank you.
Thank you.
And I'm showing no further questions I would now like to turn the call back over to Paula Ragan quick closing remarks.
Well. Thank you again for joining US today, we look forward to seeing many of you at the various upcoming investor conferences and sharing more of our scientific and clinical data in December do you have any further questions. Please don't hesitate to reach out. Thank you again and enjoy the rest of your day.
Paula Ragan: And can you kind of put in context the response data that's in there, you know, when those scans were taken, how many patients actually needed scans for response assessment, when those scans happened, and then maybe into the broader context of the time course of response that's seen with I brought in the Bruton Monotherapy?
This concludes today's conference call. Thank you for participating you may now disconnect.
Yes.
Yes.
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Yes.
Yes.
[music].
Mark Baldry: Yeah, so I'll ask Diego to take that. I mean, the big picture mark, at the end of the day, it's sort of about the kinetics of response, I think, is what you're saying. And, again, I'll turn it over to Diego to provide some more context about our data.
Diego Kadovid: Yeah, thank you, Paula and Marka. So they... The protocol originally was designed to assess the response, studying at six months and then every six months. You know, in part because you have to do whole body CT scans, which is radiation and bone marrow biopsies, we have amended the protocol to make that now more frequent every three months. I would say this update mostly reflects the six-month data, which is sort of the first look into clinical response. You know, different studies do different things, but we felt that it was important to try to get more frequent assessments, and that's why we changed it.
Diego Kadovid: Okay, thanks, that's helpful.
Operator: Thank you. And our next question comes from Stephen Willie, from Steefel. Your line is now open.
Stephen Douglas Willey: Yeah, good morning. Thanks for taking the questions. Maybe just following up on Waldenstrom's, again, understanding that the abstract cut is largely representative of what we saw at I-Eha, but can you speak a little bit about just where patients are in terms of dose escalation in this trial, specifically with respect to the 600-mig dose? And I know that there was an attention to initiate dosing maybe in cohort C at 600 migs without the step up. Can you maybe just speak to kind of where you are on the dose escalation side?
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Stephen Douglas Willey: Sure, Diego would you like to take that?
Diego Kadovid: Yeah, sure, Stephen. Yeah, so we have previously communicated, of course, that we have cleared the 200-millimeter dose and the 400-millimeter dose. We are already dosing at 600 milligrams and making much progress, and we plan to report some of that data both in the poster as well as at investor day. So yeah, that's a focus of us, to complete that enrollment. And just to remind you, once the 600 milligram dose clears in cohort B, then everybody else can be escalated to 600, including those in cohort A and all those enrolling in cohort C.
Stephen Douglas Willey: Okay. And then just on, I guess, chronic neutropenia or severe congenital neutropenia; I know these patients don't have CXCR4 mutations. But I think the intention of this program was to try to maybe correlate patient responses with some kind of genetic signature. And I was just wondering how far along you will be in that interrogation of that correlation will you be at the time of death. And I guess how much more work do you need to do in order to be able to maybe refine that patient population for responders?
Paula Ragan: Yeah, so I'll make one comment, and then I'm going to invite Art to talk a little bit more about the mechanism because I think it's really indicative of market potential. But we certainly have always been trying to help patients and physicians who understand the genetic drivers of their disease. But as we just released in our abstract, we have seen the benefit of Mavericks before broadly, regardless of mutation status, creating these multiple fold increases in white blood cells, including neuter cells and lymphocytes. So there's a huge sort of swath of patients that have the low-nutrifil counts and low lymphocyte counts that this drug could address. And then mechanistically, it makes a lot of sense.
Paula Ragan: I'll invite Arden to talk a little bit about the mechanism of GCF, which is standard of care, and how Mavericks vore really nicely synergizes with and can potentially supplement or eventually replace that. So, Art, could you chime in? Sure.
Unknown Attendee: Sure, thank you, Paul, and hi, Steve. So when we first got started with SCN, we actually understood this as a different, or a collection of different mutations that did not really include CX-Z-0-4. So the question was exactly yours, is whether or not Ricks-Fork could have any kind of benefit, and we would think that it would be connected ultimately to X-Z4 upregulation. And so we started to go through and look at all the mutations that are known, that actually do trigger some kind of nitrogen.
Unknown Attendee: neutropenia and congenital and severe congenital neutropenia or chronic metropenia, what we find is that so many of them have upregulated CXO4. And so for us, that seems to be the premise of the mechanism that when you have an upregulated CXO4, which is the underlying principle behind a lot of chronic neutropenias, then Mavericksa4 would be essentially blocking the adhesion, So that's the underlying mechanism, and it seems to correlate as well.
Unknown Attendee: with GCSF administrations, or GCSF, as you know, down regulates CXO12, and CXO4 access, and that gives you an increase in neutrophils in the peripheries. And so CXO4 antagonism is actually part of that mechanism. So it actually very much aligns with the approach that we're trying to take, and we do expect that we're going to have benefit there in a number of patients that have nothing to do with CXO4 mutations. Okay.
Stephen Douglas Willey: Okay, very interesting. They should ask the questions.
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Operator: And our next question comes from Mayank Montane, from V. Riley Securely.
Mayank Montane: Hi, good morning. This is Sahelan for mine.
Sahelan: Thanks for taking our questions. No more of them have been answered yet, so maybe just a few quick ones. In terms of the structure of the data release, how do you anticipate disclosing from the S-Diana-now broader Nutropenia program, as well as the top-line data release from the WIM program, is not going to look similar to phase two? And then maybe more on the commercial side, could you just talk about how there might be an overlap between the commercial prep for WIM and future Neutropenia indications. Any synergies that you guys are seeing on that end? Thank you.
Paula Ragan: Sure, so I think I heard sort of three or four elements of the question. So around the FCN data, we will be presenting that data in the context of some of the white blood cell and chronic administration of Mavericksa before, data that we've garnered over several trials, so that will be included in our poster, and we'll share more insights at our Investor Day on the 16th. In terms of, I think you said the WIM phase 3 data, that's certainly top line data expected in about a year.
Paula Ragan: The primary endpoint is a reminder to everyone, it's time above threshold for Nutriacil counts, and we had a 600% increase in phase 2, so that, you know, that will be, kind of the unveil a year from now when the trial is completed. And then how we're thinking in totality about building the market, you know, addressing the market of unmet need around chronic neutropenias, including WIM, we' BWIM is the landmark study to, you know, begin to build on a highly targeted population which you have heard is growing from a genetics and phenotype perspective.
Paula Ragan: And then layering on this additional patient population that's not necessarily genetically linked, but mechanistically linked, as we know, through the benefits of GCSF. Again, GCSF is a lifelong injectable product, sometimes multiple times a day for some of these patients, and we think we can just revolutionize it.
Paula Ragan: That entire field with an oral once daily, starting with WIMM and then expanding to the neutropini as beyond it. So the market, um, Footprints commercially are treated by the same doctors. It's very nicely leveraged from an infrastructure perspective and from a patient community perspective. We're learning across all types of neutropenias. So there's a tremendous amount of connectivity and leverage across the key touchpoints that we need to be to be long-term successful at the court as an organization. That's really happy.
Sahelan: Awesome, that's really helpful. Congratulations on the progress.
Paula Ragan: And I am showing no further questions. I would now like to turn the call back over to Paula Reagan for closing remarks.
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Paula Ragan: Well, thank you again for joining us today. We look forward to seeing many of you at the various upcoming investor conferences and sharing more of our scientific and clinical data in December. If you have any further questions, please don't hesitate to reach out. Thank you again and enjoy the rest of your day. This concludes today's conference call.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.
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