analysts at Piper Sandler. And before I begin, I'm required to point out certain disclosures regarding the relationship between Piper and X4, our next presenting company, which are located at the back of the room and also at the registration desk. X4 is developing CXCR4 inhibitor, mavorixafor. The FDA recently accepted the NDA for the treatment of WHIM syndrome, setting a priority review PDUFA date of April 30, 2024. Day after my birthday, so there'll be a good birthday present. And X4 is also developing mavorixafor in chronic neutropenia and will provide some updated data at ASH in just under two weeks. Here with us today is President and CEO, Paula Ragan. Thanks for being with us. Thanks, Ted. Great to be here. Paula, perhaps you can start off by describing the biology around CXCR4 and how mavorixafor works. Sure. So the beauty of mavorixafor is that it's an oral once daily treatment, and it works by a very well-validated mechanism in biology. The white blood cells, which are the army in your blood to help fight infections, are matured and mobilized through the bone marrow, and the target CXCR4 is a key chemokine receptor that enables that to happen. Certain diseases actually cause a dysfunction in that receptor and signaling pathway, and mavorixafor can correct for that. So it's a really simplistic approach, having a once daily oral to kind of boost the immune system and enable the white blood cells to get out, circulate, and do their job. Yep. So I know you get this question a lot, despite the fact that the answer's in the name. What exactly is WHIM syndrome? How serious is this? How large of an indication? Sure. So, the WHIM is the acronym for the disease, and it's a syndromic disease. So it has various aspects of clinical presentation where they have a compromised immune system. So some of them present with very severe HPV-associated warts, low immunoglobulin levels, these infections, which all these patients experience quite significantly, and the M stands for myelokathexis. The severity of the disease was really evident in our phase 3 trial. It's a very rare disease. People have not studied this well, but these patients were getting on average about five infections a year, which, if you added up the days per year that they were sick, they were sick seven weeks out of every year with some form of mild to serious infection. The beauty of the mavorixafor Phase 3 trial was that we showed that we reduced frequency, severity, and duration. All three categories were meaningfully improved with mavorixafor. For infection rate or? In WHIM syndrome, yes. Yeah. Yep, infection rate, the duration of the infections- Yep ... and then severity, all were very favorably impacted by the treatment with mav. So let's pick up on that with the phase 3 for WHIM trial. Remind us what the primary endpoint was, and the secondary endpoints, and obviously, this infection benefit was really important for the FDA. Yeah. So the phase III was a very high bar, Tier One level of evidence. It was a randomized, placebo-controlled, double-blind trial, which is a herculean effort for any size company, let alone a small one in a global pandemic. When you think about the whole world was very cautious of being exposed to infections, so our trial occurred during that entire time frame, and the amazing results of our trial shows the impact of mavorixafor. We saw, first of all, a correction in their low blood counts. These people walk around daily with very low counts of white blood cells, so the army of cells in your bloodstream that do the job to fight infections were at, you know, lower than half mast. With mavorixafor, we saw a profound correction in that, almost to near normal levels for neutrophils, lymphocytes, and monocytes, which are the three key components of your white blood cells. So those were the primary endpoint, was a specific metric called time above threshold. We had 0.0001 for our p value compared to placebo, and correcting the time above threshold or the amount of hours a day your blood had normal neutrophil counts, and that also pulled through to the other cell subtypes, lymphocytes and monocytes. And importantly, that translated into clinical benefit. Everybody was very curious, you know, how are we going to see the improvements in patients? Small study, rare disease, not well understood. But again, on every endpoint that we've disclosed, and we're still going to share some more open label extension data the first half of next year, the drug is really differentially showing a positive impact for these patients. Infection rate, severity, and duration, as we had mentioned. We even looked at types and organ systems. In all, in all factors, mavorixafor is showing a true benefit. Yeah. Yeah, really remarkable. So do you anticipate the FDA would hold an AdCom, and what are your ultimate plans to launch and market mavorixafor? Yeah. So we've already received... the NDA was accepted, and in the letter the FDA sent to us for that acceptance, stated that at this time they do not request an AdC om. So in their own words, we're not expecting an AdC om for this product. Puts us in very nice position for the April 30th PDUFA date. Yep. In terms of commercializing in the U.S., we're going to go it alone. We actually know where these patients are typically housed. It's the Immunology Non-malignant Heme. We think we can cover those physicians. We've already done some EMR research to kind of see where these WHIM-like patients are coalescing, and we think we can handle that with a very modest field force. The nice thing, too, is I believe you get a pediatric review voucher- Yeah ... with this as well, which could either be applied to future or sold to help finance the company. So what is that, what is that extra little icing on the cake for you? Yes. I mean, we, because of mavorixafor's sort of clinical benefit to date- Mm-hmm ... we did get recognized for our Rare Pediatric Disease Designation, which then translates into being eligible for a Priority Review Voucher. We're in great position to get that. It's It's kind of checking the box, and then on approval, we'll get that voucher, and likely we will monetize it. It'll be a great opportunity to non-dilutively finance the company... for about another year. They're going for around $100 million, as I'm sure- Yep ... you're familiar with, Ted, so. Yep. Nothing wrong with that. Yeah. ... Tell us how big this market is. How large of a sales force do you need? You know, what do you kind of see as the, you know, selling effort that's going to be required to really, get mavorixafor into patients? Yes. I mean, the good news is, in a lot of these ultra-rare diseases, you don't need a huge field presence, right? So I can at least benchmark off the Genzyme days. They had 2-3 dozen total field force. So this is the combination of the MSLs, and they have more specialized sales rep names for folks. But now we even have a few people on the diagnostic side and a few MSLs already in the field. We expect, you know, to hit that same type of profile, you know, no more than a couple dozen-ish, plus or minus, across the full spectrum of the company, and we do think we can reach the relevant clinical communities and patient communities with this. The good thing is also we can learn as we go. Right. Like, what you don't want to do is... You know, there's no competition. Finding patients and getting them diagnosed and on treatment is really the long game. This is a chronic lifelong therapy. You're not worried about switching in and out. Sure. You're not worried about second or third line. They just. They have nothing. Just so that we ask, what about drug supply? Is there anything tricky to this? You know, how do you sort of plan out the campaigns to- Yeah Make sure that when you do get patients on therapy, they can stay on it? Yeah. So, hearken from my Genzyme days, we're very familiar with trying to make sure you get supply and demand correct. So we're well positioned for that. Good. We have our supplier in the U.K., Aptuit/Evotec, a local manufacturer- Mm-hmm -in the States for the drug product. And certainly, we know even with our batches that we're planning to validate with for the FDA, we're in excellent position- Good to have not only inventory, the right levels of inventory, but certainly supply the market over the next few years. And again, an ultra-orphan indication, I can imagine, you know, it's going to carry a high price tag, right, rightfully so. How important is reimbursement here? How do you kind of jump through all of those hoops- Yep that really go along with the launch? Yeah. So, I mean, we're already working on... I mean, similar to the clinical community, you work with the payer communities- Good to begin education and awareness. Certainly, with our new phase 3 data that we just unveiled in May- Good There's a part of that, part of that is socializing it with the payer systems. You're right, or ultra-orphan pricing does command those very high price points, but it's because typically these drugs are disease-modifying. And as, you know, we certainly think the phase 3 data support, this drug is really having a tremendous impact on this ultra-orphan population. Yeah. And are these patients expensive to treat? Yeah. So interestingly, again, not a lot of good natural history studies, but some of the patient foundations have done studies on what is the total healthcare impact of these patients. Again, and they're not doing well. Right. So these are the hospitalizations, lost days of work. Some of them, there are some deaths, certainly due to immunocompromised- Yeah -patients. In LIM, specifically, we have less information, but their disease profile is no different than what some of these other immunocompromised patients have, and they were in the $150,000-$200,000 per year- Yeah just for baseline, and that's living the life that they're living, not really having any, you know, normalization of their health. Yeah. Yeah. Now, your second indication is chronic neutropenia. So what's the clinical need here, and how does mavorixafor... I mean, obviously, the same mechanism, how does it benefit these patients? Sure. So the interesting thing about Chronic neutropenia, it is a better understood and validated patient population, right? There's ICD-10 codes for this population. There is one approved treatment for this patient population- Mm-hmm So we know more what their diseases represent. Very severe infections. They actually get a lot of oral mucosa infections where and ulcers, which are incredibly painful. They do wind up in the emergency rooms. One of our patients that we've spoken to, his first presentation was meningitis, where he was almost comatose. Right. So the unmet need, I mean, think about the severe end of infections and how that can drive patients into the hospital system. Yeah. And then G-CSF did help that, for sure. It's a drug that is very solidly helpful on efficacy. It is very challenging for every aspect of the drug that needs to also occur. There are some chronic toxicities, including increased cancer risk. There's massive bone pain, and frankly, most of these patients are either not treated at all or they're undertreated with this drug, so they're getting the partial benefit of a drug, which is helpful, but we believe mavorixafor is going to certainly up the game overall on all counts. Yeah. I think it's time to move past G-CSF. Yeah. So you reported some data on the first three patients. Tell us about this preliminary data. What more should we expect at Hematology in just two weeks? Yeah. So the phase II study, which is more than three patients, it's a couple dozen patients- Good was designed to answer two questions. The first question is: Do we have a durable effect on neutrophil counts, right? We saw that very robustly in the WHIM patients. Hopefully, we see the same in CN. So our August update was a first glimpse into 3 patients. We had at least 3 months of data on all of them, and we saw a very positive, durable effect. So that wasn't a newsflash to us. The drug nicely mobilizes and increases the white blood cell count. The second piece of the puzzle is: What can we do to improve the G-CSF utilization by pulling it off? So these 3 patients at ASH now will have the full 6 months of data. We'll be able to see how the patients were titrated up or down G-CSF, and hopefully, what we want to do is move to a better place. All patients want to reduce their G-CSF exposure. We certainly expect that we have that trajectory already, even based on the August data. Yeah. Again, it's three patients, but we think those anecdotes will be helpful to demonstrate the full spectrum of what the drug might be able to do. Now, you've already talked about even just based on this early signal, and again, all that you know about mavorixafor, to move into phase 3 trials in chronic neutropenia. Tell us about these plans. When could you start that study? We are heads down and moving forward towards initiating that trial the first half of next year, as early as possible. There's nothing rate-limiting at this step, so we've completed our agency discussions. We even agreed upon trial design, including two primary endpoints around infection rates and neutrophil response. We've powered it robustly, and now we're frankly contracting with the CROs and getting the sites open. So we're very nicely on track to meet that expectation, nicely. How large do you think this study would be? You mentioned the two primary endpoints in terms of ANC response and, and infection similar to before. How large do you think that study would have to be? Yeah. So we have disclosed we, we have, 150 patients that are the target, total size of recruitment numbers, and that'll be balanced across the two arms, and that will give us at least a 90% power on both of those. So the 90% plus power on the infection rates and even in a much higher power on the neutrophil count. So we're very well positioned. It's very much like a WHIM trial, rinse and repeat. Right. The WHIM trial was very successful on the 30 patients. We're obviously going up to larger numbers, one- Right - because it's a bit more heterogeneous, and then 2, we're really overpowering it to, to demonstrate success in that infection rate. And how do you layer in that G-CSF taper? Because that has to be kind of controlled to do it correctly. Correct. How does that get factored into the trial? Yes. So we are not. There will be no taper of G-CSF in the trial, so everyone who comes on G-CSF needs to maintain a G-CSF. Yes. The only rare instance of modifying G-CSF dose would be for safety reasons, if their neutrophil counts are sustained at exceedingly high levels, and an independent safety committee will review that and then suggest any down titration. The good news is that as long as you're above 1,500, there's really no differential, so we don't... If, if there are any changes, we don't expect them to impact anything clinically, because they'll always be within normal limits. Enrollment criteria, these are neutropenic patients on G-CSF or off G-CSF, it doesn't matter? Correct. And then you will measure change in neutrophil count and also infection rate over time for- Correct. Correct. It's really not looking at the taper. That's correct. Okay. Taper will be a different study. Yeah. Tapering is something where we'll learn some insights from this ongoing phase two. Yeah. Then ultimately, we believe the future state is with the phase 3- Yes If it's approved off of these data, the label will likely read: "For treatment in chronic neutropenia patients, autoimmune, cyclic, or congenital or idiopathic, with infections, with ongoing infections. Right. It won't be contingent upon G-CSF. We do want to help the community figure out how to safely down titrate folks. Yeah. We'll be doing that. We're exploring that right now in the phase 2, and we'll need to do some more work longer term. Cool. That's really helpful. Yeah. So obviously, chronic neutropenia is a much larger market than WHIM. You know, how do you anticipate marketing mavorixafor for this indication? It's a good problem to have to aspire to. You're gonna have a lot of experience already with, you know, a focused sales force. Would this require a partner? So that's a great question. I think, still in the U.S., I mean, the beauty of WHIM is it's really like a segue into chronic neutropenia. Yeah. The similar treaters, similar unmet need. We hope similar data sets when the CN and phase 3 finally yields out. And so I think it's actually a very nice journey to bringing the first and only oral treatment- Yeah to a group of doctors and patients who need something that's not injectable and some choice. They literally, most of them, have maximum one choice. Yeah of medication these days. So we're bringing choice. In terms of the U.S., I think we can handle. Ex-U.S. is always a different kettle of fish. Certainly, it depends on. I think for us, as we think about, let's say, the EMA submission from a regulatory perspective- Yeah We're on track for about a year from now. The beauty of between now and a year from now is we can see where we're at with chronic neutropenia data. Sure. I think ex-US partners are also kind of very interested in that because I don't think they see the opportunity as just WHIM, but also see WHIM and CN as a great opportunity in totality. So for us, ex-US strategy off of the EMA is a little bit TBD- Yeah And we'll get to make that decision with more data. Yep, that's really helpful. So I just want to pause, see if anyone has any questions. We've really marched through this very efficiently and expeditiously. Now, I know you guys ended the third quarter with over $142 million in cash. How long does this fund the company? Does it enable you to get to approval and launch? Yes. So that financing, our current cash position, gets us into 2025, Q1 of 2025, and that's not including a PRV sale- Yep - which we certainly hope to monetize midyear next year. And we also have some debt availability, which is about another $30 million, including approval. There's some contingencies on milestones, but we would certainly expect that to be available midyear as well. Awesome. Great. Well, thank you, Paula. Yeah. Thank you. Really exciting time. I'm looking forward to the data at ASH, but obviously fuller update next year. Yeah. Good luck heading into the PDUFA date. Thank you very much, Ted. Appreciate it. Cheers. Thanks for the time. Thank you. Thanks everybody.