X4 Pharmaceuticals, Inc. Common Stock Investor Day 2026

Thank you, Remy, and thank you all for joining us this morning. We have a great lineup of speakers today and appreciate the key opinion leaders joining us to share their expertise on the treatment of primary chronic neutropenia. With me today is John Volpone, our President and Chief Operating Officer. John brings more than two decades of drug development leadership across oncology and rare disease. Most recently, he was Executive Vice President and Chief of Staff at CTI BioPharma, and before that, he held business development roles at Bristol Myers Squibb and ZymoGenetics. We also have David Kirske, our Chief Financial Officer, with us today. David has 20 years of strategic financial and operational experience, most recently as CFO of Stratus Therapeutics. Prior to that, David was Executive Vice President and CFO of CTI BioPharma, where he played a central role in the Sobi acquisition.

I'm pleased to introduce Michael Marcello, our Senior Vice President of Market Strategy and Development. Michael has nearly 30 years of commercial medical experience in biopharma and has led more than 12 commercial launches in hematology, oncology, and rare disease at companies including CTI BioPharma, Amgen, Onyx, Lilly, and Seattle Genetics. Most recently, Michael was Global Head of Commercial Strategy and Vice President of Markets at Autolus, where he helped lead the launch of the company's first cell therapy. We're also honored today to have Dr. Julia Warren, a pediatric hematologist and physician-scientist at CHOP Hospital of Philadelphia, with us, and she's an Assistant Professor of Pediatrics at Penn's Perelman School of Medicine. Dr. Warren sees patients in CHOP's comprehensive bone marrow failure center and Cancer Predisposition Clinic programs, with a specialized interest in patients with chronic neutropenia.

Finally, we welcome Dr. Shreyans Gandhi, a consultant hematologist at King's College Hospital in London. Dr. Gandhi is focused in the field of myeloid disorder. His practice is focused in the field of myeloid disorders with a primary interest in bone marrow failure, cytopenic disorders, and PNH, including cellular therapies and stem cell transplantation. Please note Dr. Warren and Dr. Gandhi are consultants to X4, and the views they express today are their own. For reference, you can access speaker biographies on the right side of the screen or via the button in the top right-hand corner. First of all, I'll go through the agenda today. Once I've finished with the opening remarks, John Volpone will present the mavorixafor clinical program. He'll update you on the 4WARD trial and introduce to you for the first time the 4STEPS trial of dose adjustments of G-CSF in the presence of mavorixafor.

We will then move on to the market opportunity in primary chronic neutropenia, presented by Michael Marcello, who will present to you today our market research that has established the market opportunity for mavorixafor for chronic neutropenia. Following Michael's presentation, we'll move on to a fireside chat, which I'll host with Dr. Shreyans and Dr. Gandhi, Dr. Gandhi and Dr. Warren, and then we will move on to a Q&A session where you can ask questions. With that, I'd now like to turn the call over to John to discuss our mavorixafor clinical development program. John? Apologies. Yes, you're absolutely right. I forgive you. The aim of the company is to deliver on the promise of CXCR4 antagonism through mavorixafor. To do that, the company's had to go through quite substantial corporate transformation, as many of you know, in 2025 and 2026.

We're now able to focus on the completion of the pivotal Phase III 4WARD trial in primary chronic neutropenia. We aim to complete full enrollment by the end of Q4 2026 and expect top line on the primary date in Q1 2028. If successful, that could lead to a U.S. FDA approval in late 2028 or 2029. This year, we've also been working on the Phase II trial, the 4STEPS program that I mentioned earlier, and that's a trial to demonstrate if we can safely reduce G-CSF dose in patients with chronic neutropenia following the initiation of mavorixafor. Next slide, please. Mavorixafor is an oral agent designed to alleviate neutropenia. Its target is CXCR4, which regulates the movement of white blood cells throughout the body.

If CXCR4 is antagonized with an agent such as mavorixafor, it results in white blood cell migration from the bone marrow into the circulation. As a result of that, the mavorixafor increases the levels of neutrophils and lymphocytes in the bloodstream. It is this effect that we believe will have an impact on infections in patients with chronic neutropenia, and this is what we are testing in the Phase III 4WARD trial. Next slide. I would like to introduce John Volpone, who is going to present the clinical program.

Thank you, Adam. I will begin with an overview of our pivotal Phase III 4WARD trial in primary chronic neutropenia, or PCN, and then introduce 4STEPS, our Phase II study designed to evaluate whether G-CSF dosage can be safely reduced in patients who have started treatment with mavorixafor. 4WARD is a global double-blind, placebo-controlled trial with a target enrollment of 126 patients. We designed the inclusion criteria to enroll patients in whom a potential treatment benefit can be clearly measured. Participants must have a diagnosis of congenital, autoimmune, or idiopathic chronic neutropenia, or an absolute neutrophil count, or ANC, below 1,000 cells per microliter. This is defined as moderate or severe disease. Participants must also have at least 2 infections requiring intervention in the previous 12 months. These are patients with serious recurrent infections who need better therapies to manage their disease.

Patients are randomized 1-to-1 to receive mavorixafor or placebo, in each case, with or without G-CSF. ANC is assessed at baseline and at months 1, 2, 3, 6, 9, and 12. The trial has 2 primary endpoints, ANC response, defined as an ANC above 500 cells per microliter, and annualized infection rate. With 126 patients, the study is powered at 93% and 89% respectively for these endpoints in the intent-to-treat population. Secondary endpoints include severity of disease of infections, antibiotic use, fatigue, quality of life, and safety. We expect complete enrollment in the fourth quarter of this year, with top-line data expected by the end of the first quarter of 2028. Now I would like to share the baseline patient characteristics for 4WARD based on blinded pool data as of September 2026.

Enrollment is evenly divided between moderate and severe disease, with median age of participants in the trial at 36 years old and 70% of participants are female. Median baseline ANC is 483 cells per microliter, well below the trial's entry criteria of 1,000. 68% of participants have 3 or more infections at baseline. 4WARD requires at least 2 infections in the prior 12 months for entry, so this is a population with a meaningful burden of infection. 37% of participants are on concurrent G-CSF. As a reminder, we are evaluating mavorixafor as both a monotherapy and in combination with G-CSF. Importantly, we have not seen any new safety signals to date. Taken together, these baseline characteristics give us confidence that we are enrolling the right patients in 4WARD and the patients we believe stand to benefit the most from an oral treatment option.

Today, I would like to introduce our planned 4STEPS clinical trial that is designed to complement 4WARD. In 4WARD, patients who enter the study on G-CSF keep the same G-CSF dose for the entire study, so any clinical benefit of mavorixafor can be clearly measured. However, with real-world usage, we expect that patients and physicians will want to reduce the use of G-CSF once mavorixafor is started, citing the burden of frequent injections and side effects such as bone pain and fatigue. 4STEPS is designed to evaluate whether G-CSF dosage can be safely reduced while maintaining stable neutrophil counts after mavorixafor has been started. 4STEPS is a single-arm, open-label, multi-center, phase II study. We plan to enroll approximately 25 patients with acquired primary autoimmune or idiopathic chronic neutropenia.

Patients must be on stable G-CSF therapy at study entry and have a baseline ANC of at least 1,000 cells per microliter, which makes this a different population for 4WARD. The study will be conducted at approximately 25 sites in the U.S. and the U.K. The primary safety endpoint is the safety and tolerability of mavorixafor. There are three primary efficacy endpoints, each measured at six months. The percentage of patients who stop G-CSF entirely, the percent reduction in average daily G-CSF dosage, and the percentage who reduce their G-CSF dosage by 75% or more. Here's how the study is designed. Patients start with a four-week observation period on G-CSF alone. Mavorixafor is then added for an eight-week run-in, which gives it time to reach its full effect. Next comes a stepwise G-CSF reduction period of 16-20 weeks.