Morning, or rather good afternoon now. Welcome to the Jefferies Global Healthcare Conference. My name is Tim Odutola, part of the Jefferies Healthcare Team, and it's my pleasure today to introduce Adam Craig, chairman of X4 Pharmaceuticals.
Thank you, Tim, and thank you to the Jefferies team for the invitation to join you today. I will be making some forward-looking statements during the presentation today. I refer you to the text in this slide. X4 Pharmaceuticals is primarily a Boston-based company that specializes in rare hematology conditions. Our lead asset is a drug called mavorixafor, which is already approved in the ultra-rare indication of WHIM syndrome, both in the U.S. and in the European Union. We're currently focusing on a second and broader indication in chronic neutropenia. We have a phase III trial called 4WARD underway that we expect to complete enrollment at the end of the third quarter of this year and top line data in 2027 with hopefully an approval for second indication in 2028. X4 Pharmaceuticals over the summer of last year, August of last year, underwent considerable corporate restructuring.
There was an introduction of a new management team, myself, my colleague David Kirske. Sorry, could I have the slide back to where it was there, please? Because that's the only screen I can see. Thank you. Much appreciated. New restructuring of a team from CTI BioPharma. Some of you may know we led the team with the successful acquisition of CTI BioPharma and Sobi in 2023. When we came in, we had to reduce the headcount to reduce costs, and we reduced it by 50%. We changed the C-suite, and we now, having raised $240 million in two raises last year, we now have enough cash to take us through commercialization to the end of 2028. Mavorixafor is an oral agent that's designed to alleviate neutropenia. Neutrophils are moved around the body through a target called CXCR4, and mavorixafor is an antagonist of that target.
Through the target, when it antagonizes the target, neutrophils are released from the bone marrow into the bloodstream. In patients who have low neutrophils and are susceptible to infection, this can be quite a significant change. It can reduce their risk of infection, as I'll talk about later in the presentation. Mavorixafor has already been reviewed by the FDA, and it's been shown to increase neutrophils and also circulating lymphocytes. Chronic neutropenia is a difficult situation to live with, a difficult condition to live with. Hopefully, most people in this room will have neutrophil counts above 1,500, which is the normal level. If you have neutrophil counts lower than that, if you have severe neutropenia, where your counts are 500 cells per microliter , or moderate, where they're 500- 1,000, you're at risk of increased infections.
These infections really can be quite debilitating, often require hospitalization. They can potentially be fatal. They're very limiting to people's lives because just going out of your home, going into society as a whole, you're at risk of infections. It's quite a difficult condition to live with. Our aim is to make the lives of these patients a lot better. We've done a fair bit of work on the population. We estimate through IQVIA claims analysis and some physician survey work that we did with ClearView Partners, that there are 57,000 patients in the U.S. who have primary chronic neutropenia. I should be clear, that's not including patients who get neutropenia from things like chemo. That's a secondary cause, and that's a much bigger population. Of that 57,000, there's 22,000 patients who have recurring infection.
If you take our population that we're studying, which is the moderate and severe disease patients with an ANC less than 1,000, that's 15,000 patients. That's our target population. A significant number of patients, and certainly given our specialty in dealing with unmet medical needs, a very important population to deal with. What are the unmet medical needs in chronic neutropenia? It's really very much determined by how patients and whether they're symptomatic. It's also determined by how patients, whether they're on G-CSF and how they respond to G-CSF. We think there's an opportunity for mavorixafor to be used as a single agent in patients who haven't used G-CSF or were intolerant of it, weren't able to take it, they felt unwell, they had bone pain.
Or for those who are on it, hopefully to reduce the bone pain by reducing the G-CSF dose and reducing the long-term risk of malignancy. One of the things we have surveyed in our physician survey, we asked, "What are the most important things for a new therapy in chronic neutropenia?" It probably comes as no surprise that an oral therapy is the number 1 desire of new physicians for a new therapy is an oral therapy. That's because G-CSF is an injection, it can't just be given as easily as a tablet, whereas mavorixafor is an oral agent, it can be given once a day. We have some proof of concept data. 23 patients. That phase II study that was already conducted when David and I joined the company. What they looked at was really this data set. Although small, really answers two questions.
Can mavorixafor be given in chronic neutropenia as a single agent and increase neutrophil counts? The second is can it be given safely with G-CSF, and can G-CSF doses be reduced while still maintaining neutrophil counts? 23 patients, 15 of them were idiopathic, 10 of the patients were given mavorixafor alone, and 13 were given mavorixafor in combination with G-CSF. If you look at the monotherapy patient, you can see here at baseline, the mean ANC was less than 1,500 on the left-hand side. When the drug was given over a one to six-month period, the ANC was at 1,500 or above. This demonstrates that mavorixafor alone can increase the ANC. If we look at the G-CSF question, remember the question was can you change the dose of G-CSF safely and can you give the drug safely in combination? The answer is yes.
The mean G-CSF reduction in the G-CSF patients was 70%. In fact, three patients managed to come off G-CSF and still maintain their counts. If we look at the data here, now, this is the green box, the lower part of the green box. The green box is showing a normal range for ANC. The objective here is to maintain the ANC whilst G-CSF doses go down. As you can see, over a six-month period from left to right, despite significant reductions in G-CSF dose and the elimination of the dose in some patients, the ANC was still maintained within normal range. A very powerful, very important finding. Obviously, every drug has to be viewed on the efficacy side and also the safety side. We have found to date that the drug is pretty well-tolerated.
There is some GI toxicity, nausea and diarrhea in the first few weeks of therapy. Most patients it resolves with over-the-counter medication. As we enroll more patients on the phase III and we see more patients, we haven't seen any new signals from the early trials. We haven't seen any new indications of toxicity, which is a good position to be in. This is the trial that 99% of the time and resources of the company are spent on, which is the 4WARD, the phase III trial in chronic neutropenia. What we're aiming here is to get a second indication for the drug in the U.S., which is much larger and potentially more valuable to the company than the WHIM indication. 4WARD is a double-blinded, placebo-controlled study. Patients are split between two arms, mavorixafor plus or minus G-CSF and placebo plus or minus G-CSF.
We're including congenital, autoimmune, idiopathic patients, and we have co-primary endpoints. The first is a reduction in the annual infection rate as independently assessed by a blinded committee, and then the other one is an increase in ANC of at least 500 cells per microliter. Both endpoints are very well powered, greater than 96% for the ITT population. We do have some other interesting endpoints. I'll point one out to you, which is fatigue. We have quite a few anecdotal reports of improvement in fatigue and patients feeling better on mavorixafor in the early phase studies, and this is something we're looking at in the phase III trial. When we joined in August of last year, enrollment was an issue for the company. Since that time, we have expanded our clinical trial to 110 active sites. We've opened sites in the U.S.
We have over 20 sites in the U.S. We moved our Medical Science Liaisons from commercialization of WHIM to the recruitment activities for the trial. We've worked on getting dedicated patient referral mechanisms from hospitals to our treatment sites. We've consolidated our CROs to improve efficiency, and we continue to use tools, including some AI-driven tools to identify new patients. Because this is obviously a rare disease, 15,000 patients is our population in the U.S., so we have to work hard to find the patients. On the financial side, before I summarize, our cash position is strong thanks to the prudent cost management by David Kirske, our CFO. Currently, we last reported $233 million in cash, and that's based on 144.8 million fully diluted shares outstanding. Just to finish, this is a short presentation. We are on track to deliver data in the second half of 2027.
This will be done by a new C-suite team who specialize in hematology, drug approval and drug launch. We are now supported by blue -chip investors, we have cash runway through 2028. We already have clear proof of principle of the role of mavorixafor in increasing neutrophil counts from our phase II study and from the WHIM studies. The 4WARD study is the registration study to get the new indication approved with the FDA. We're on track to have a FDA submission and probably approval in 2028. This is a pretty large opportunity. It is around 15,000 patients. There's certainly a clear unmet medical need, I do believe very strongly a well-tolerated oral agent would be very useful in this setting, either as monotherapy or as combination. That's it. Thank you for listening to the presentation. Tim.
[Break]
Thank you, Adam. We can now open up for questions. We can pass the mic around. Please just raise your hand, and Jefferies will bring a mic over to you shortly.
Thanks for the presentation. Are there possibility for indications beyond the one you're going for now?
Yes. The question was, are there possibilities for indications? Absolutely. I have quite a long list in my head. The priority at the moment is to get the enrollment completed in the trial. What we hope to do in 2028, maybe through some ISTs and other programs, is increase the use of drug and generate data in other areas before we launch the second indication in 2028. Absolutely, there are a number of other neutropenias that we think we could get some very interesting data in. As of today, it's not a priority. We're focusing the company on the execution of the 4WARD trial.
Thank you.