X4 Pharmaceuticals Inc 4WHIM Phase 3 Clinical Trial Update Call Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Ted Tenthoff - Piper Sandler & Co. - Analyst : Great. Thank you very much. Can you hear me okay?

Question: Ted Tenthoff - Piper Sandler & Co. - Analyst : Great. Well, thank you for just a fantastic presentation today. I really appreciated all the detail, both from the clinicians as well as the patients, on what it's really like to experience WHIMS. And I have two questions, if I may. They're a little bit different. But firstly, how much does it cost to care for a WHIMS patient? Do we have that kind of data? And how relevant are those cost savings going to be for potential payers who will ultimately reimburse us? And I was intrigued to see the flip side of the mechanism of actually having some skin issues. I don't think they were too severe. And I just wanted to ask the physicians who are logged in if that raises any questions or if that might require any monitoring on their part just to keep an eye on any kind of autoimmune-like syndrome. Thank you so much. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 16, 2023 / 8:00PM, XFOR.OQ - X4 Pharmaceuticals Inc 4WHIM Phase 3 Clinical Trial Update Call

Question: Ted Tenthoff - Piper Sandler & Co. - Analyst : Just with respect to the -- I guess, is there any way that we could actually promote almost autoimmune-like syndrome if we turn on the immune system too much? Teresa Tarrant - Duke School of Medicine - Associate Professor & Vice Chair, Translational Research in Rheumatology & Immunology Okay. I think I'm -- if I'm understanding correctly, it's, can one develop autoimmune sequela from being on chronic administration of mavorixafor? Is that -- am I paraphrasing correctly?

Question: Ted Tenthoff - Piper Sandler & Co. - Analyst : That is incredibly helpful. I appreciate your time and perspective.

Question: William Wood - B. Riley Securities, Inc. - Analyst : Hi. Thanks for taking our questions today, and many congratulations on the impressive infections data disclosure today. On your FDA interactions, glad to hear you've had a pre-NDA meeting already. And I'm wondering if you were able to get any insights on how they may think similarly or differently about severe chronic neutropenia relative to WHIM, in terms of choice of ANC endpoint but also the relevant clinical outcomes. I know there have been some GCF studies done in CN. Whereas, obviously, you didn't have insight in WHIM, although they are quite old. So maybe if you just give us any extra color there, that'd be helpful. And then one follow-up.

Question: William Wood - B. Riley Securities, Inc. - Analyst : Excellent. I really appreciate that. And then for the second question for the experts, the infection data looks quite impressive in different ways you look at it. Are you able to provide some more color on how the wart disease burden is being thought of? And maybe if you could also characterize the skin adverse events that were noted here. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 16, 2023 / 8:00PM, XFOR.OQ - X4 Pharmaceuticals Inc 4WHIM Phase 3 Clinical Trial Update Call

Question: William Wood - B. Riley Securities, Inc. - Analyst : Got it. I appreciate that extra color, and congratulations again on the great information we saw today. Thanks for taking our questions.

Question: Kristen Kluska - Cantor Fitzgerald & Co. - Analyst : Hi, everyone. Let me also add my congratulations. And it's really great to see in perspective what it does for the patients, hearing from them directly. So appreciate those comments. The first question I have for you is, hearing some of these patients' stories, it seemed the theme was clear that over time, they were experiencing a number of infections. And they got diagnosed around their teenage years, early 20s. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 16, 2023 / 8:00PM, XFOR.OQ - X4 Pharmaceuticals Inc 4WHIM Phase 3 Clinical Trial Update Call So I wanted to ask -- and I know the X4 team's doing a lot of work on patient awareness. But how do you think that adding a potential therapy to the market, driving awareness, is going to potentially lead to some of these patients perhaps getting diagnosed earlier?

Question: Kristen Kluska - Cantor Fitzgerald & Co. - Analyst : Thank you for that. And then looking at the specifics, across the board, there was quite a number of different infections. And some of your thought leaders highlighted that the lungs and bacterial, in particular, are some of the more problematic. But wanted to ask if the patient population in this is what you would expect in real life, meaning, the types of infections that you saw the most. You also highlighted that this was during the COVID-19 pandemic, some of the enrollment. So I'm wondering if that played into a role at all as well. Thank you again.

Question: Kristen Kluska - Cantor Fitzgerald & Co. - Analyst : Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 16, 2023 / 8:00PM, XFOR.OQ - X4 Pharmaceuticals Inc 4WHIM Phase 3 Clinical Trial Update Call

Question: Stephen Willey - Stifel Nicolaus - Stifel Financial Corp - Analyst : Hi. Can you guys hear me okay?

Question: Stephen Willey - Stifel Nicolaus - Stifel Financial Corp - Analyst : Sorry about that. This was great. Thanks for the excellent presentation. Maybe just for the attendant physicians, just curious how you would juxtapose the difficulty of improving infections in a WHIM patient versus, I guess, a more typical CN patient with a non-congenital subtype. I know WHIM's obviously a more complex form of CN, but just trying to think about the read-through of this data into a broader CN population. And then maybe just as a follow-up, would you expect the kinetics of infection rate improvement to be similar in CN as well, whereby you're seeing most of the benefit occurring after three to six months of treatment?

Question: Stephen Willey - Stifel Nicolaus - Stifel Financial Corp - Analyst : Okay. That's helpful. I know the company talked about kind of what they're doing on the disease awareness and genetic testing efforts. But, I guess, just given the underlying variability of the morbidity associated with this disease, can you also speak to approximately what proportion of patients identified would you expect to be candidates for therapy? Is this something that you're giving to all confirmed WHIM diagnoses?

Question: Stephen Willey - Stifel Nicolaus - Stifel Financial Corp - Analyst : I'll squeeze in one quick -- one question. So I know there wasn't a reduction in, I guess, pre-existing wart burden, per se. But I know that we've heard from a couple of the physicians just about the impact of secondary malignancies that are caused by HPV infection. And I'm just curious if there's going to -- if there would be any attempts to serotype HPV in these patients and whether or not you would expect to see a reduction in the oncogenic HPV strains 16 and 18, and I guess how important would that be to the overall value proposition. Thank you.

Question: Stephen Willey - Stifel Nicolaus - Stifel Financial Corp - Analyst : All right. Thank you very much.

Question: Marc Frahm - Cowen and Company, LLC - Analyst : Thank you, and congrats on the data and your really strong infection reduction. During the presentation, you discussed reductions in antibiotic use. Were any changes seen in IBIG use also?

Question: Marc Frahm - Cowen and Company, LLC - Analyst : Okay. Thanks. And then maybe just if there's any more details you can provide on the severe infections that were seen. And maybe if they happen to be, Dr. Tarrant, any of your patients, just any color you can give on kind of the difficulty of managing some of these infections that are seen.

Question: Marc Frahm - Cowen and Company, LLC - Analyst : And then maybe -- Dr. Tarrant, you touched on this a little bit. Just maybe some rational hypotheses as to why the wart burden didn't change. Can you speak more to the difference between kind of the infections that were being seen -- the respiratory infections and things like that -- that were certainly going down versus warts? And maybe Dr. Shimamura, just how you think about that for when we look at the CN indication for the types of infections you have to worry about and what that means for those types of patients. Teresa Tarrant - Duke School of Medicine - Associate Professor & Vice Chair, Translational Research in Rheumatology & Immunology I'll go first, and then I'll let Dr Shimamura. So with respect to warts -- and that's kind of what I'll speak to as opposed to chronic neutropenia, which is Dr. Shimamura's area. So with respect to warts, if you break down what type of immune cells fight against HPV versus what types of immune responses fight against bacterial infections, they are very different arms of the immune system. So in terms of what fights infections quickly, it's antibodies and it's neutrophils. Those are your kind of first-in-line host defense to respond quickly to infections. So you're looking at responses, then, of your drug on aspects of the immune system that work quickly versus aspects of the immune system, like T cells, which are more involved in the antiviral response. There may be different kinetics of the drug and its effects on different subpopulations of the immune response. When you get a bone marrow transplant -- and Dr. Shimamura is going to talk more about that, probably. But when you get a bone marrow transplant, immune cells come back at different rates. T cells are some of the last to come back and behave normally. So here, we've got a drug that's working on all immune cells. Because all immune cells have CXCR4 on its surface; and all immune cells are responding to CXCR4 in the way that they migrate, and the way that they proliferate, and the way that they leave the bone marrow. It's just a natural part of how immune cells get around the body and move between spleen and bone marrow and where they need to go. So those responses are probably subtly different in different immune cell subsets. And so my hypothesis would be that it's having a differential response on T cells, which is more important in HPV host defense. And that may be something that takes longer for that to happen than where you'd see a neutrophil response or an antibody response. But I'd be delighted to hear more from Dr. Shimamura and her perspective.

Question: Marc Frahm - Cowen and Company, LLC - Analyst : Thanks, very helpful. And congrats again on the data to the team.

Question: Swayampakula Ramakanth - H.C. Wainwright & Co. - Analyst : Hi, Paula. Can you guys hear me? Thank you for doing this, and congratulations on the data. And certainly, a great discussion so far. Obviously, a lot of the aspects of the drug and the benefits have been discussed. But as physicians on the panel, if you're thinking about the overall clinical benefit, because that's what is basically going to be looked at by the regulators, what is clinically meaningful for these patients? Because we kind of talked a little bit about -- we talked a lot about infections, a little bit of other secondary issues or concerns that this drug really helps out with. But overall, what are the aspects that, as a regulator and as the clinicians who help the regulators, you folks want to see? And if you can discuss through that clinical meaningfulness, that would be helpful, just to see an oral aspect of it.