X4 Pharmaceuticals, Inc. · NASDAQ:XFOR

X4 Pharmaceuticals — Technical Presentation (May 2023)

20 slides from X4 Pharmaceuticals's technical presentation, May 2023

1. Slide 1: Results of a Phase 3 Trial of an Oral CXCR4 Antagonist, Mavorixafor, in WHIM Syndrome

   Results of a Phase 3 Trial of an Oral CXCR4 Antagonist, Mavorixafor, for Treatment of Patients With WHIM Syndrome Raffaele Badolato, MD, PhD1; Jean Donadieu, MD, PhD2; In Collaboration With 4WHIM Study Group 1Department of Clinical and Experimental Sciences, University of Brescia & ASST Spedali Civi

2. Slide 2: Disclosures

   Raffaele Badolato, MD, PhD Disclosures • Is a current employee of the Università degli Studi di Brescia • Is a consultant for X4 Pharmaceuticals, Angelini, and Janssen • Has an interest in Sobi (IDMC) Professor of Pediatrics Chair of Pediatrics, ASST Spedali Civili di Brescia Chairman Post-graduate

3. Slide 3: 4WHIM Study Group

   4WHIM Study Group Author Affiliation Author Affiliation Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Queensland Children’s Hospital, South Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Jane Peake, MBBS Laia Alsina, MD, PhD Brisbane, Queensland, Australi

4. Slide 4: WHIM Syndrome At-a-Glance

   WHIM Syndrome At-a-Glance WHIM Syndrome A rare immunodeficiency disease that can present with chronic neutropenia, lymphopenia, monocytopenia, and/or recurrent infections, including warts, resulting from impaired leukocyte trafficking predominately caused by gain-of-function variants in CXCR41,2 Pre

5. Slide 5: 4WHIM: Phase 3 Trial Design

   4WHIM: Phase 3 Trial Design (NCT03995108) Primary End Point Assessed Mavorixafor (n=14) Rollover to Screening (>50 kg, 400 mg QD; ≤50 kg, 200 mg QD)a open-label 1: 1 Baseline extension Randomization visit (treatment) Placebo (n=17) (n=27) Primary end point First key secondary end pointc Other second

6. Slide 6: Time Above Threshold as an End Point

   Time Above Threshold as an End Point TATANC and TATALC • Clinically relevant end points7 • Used to predict the risk of serious bacterial infections in patients with neutropenia and lymphopenia, resulting from disorders of bone marrow production7 Calculation of TATANC TATANC = Time above threshold 75

7. Slide 7: Key Demographics and Baseline Characteristics

   Key Demographics and Baseline Characteristics Mavorixafor Placebo (n=14) (n=17) Adolescents 12 to <18 y, n (%) 7 (50) 8 (47) Adults ≥18 y, n (%) 7 (50) 9 (53) Sex, female, n (%) 9 (64) 9 (53) Previous immunoglobulin usage, n (%) 6 (43) 8 (47) Screening ANC (cells/µL) Mean (SD) 173 (112) 194 (123) Me

8. Slide 8: Trial Met Its Primary End Point

   Primary End Point Trial Met Its Primary End Point Mean TATANC Over 52 Weeks in Intent-to-Treat Populationa 25 P<.0001 LS mean TATANC, hb,c P=.0002 P<.0001 P=.1019 20 15 Mavorixafor 10 Placebo 5 0 Week 0 13 26 39 52 Mavorixafor n: 13 13 11 9 10 Placebo n: 16 16 17 17 17d Overall, mean TATANC was 15.0

9. Slide 9: Trial Met Its First Key Secondary End Point

   First Key Secondary Trial Met Its First Key Secondary End Point End Point Mean TATALC Over 52 Weeks in Intent-to-Treat Populationa 25 P<.0001 P<.0001 LS Mean TATALC, hb,c P=.0099 20 P<.0001 15 Mavorixafor 10 Placebo 5 0 Week 0 13 26 39 52 Mavorixafor n: 13 13 11 9 10 Placebo n: 16 16 17 17 17d Overa

10. Slide 10: Reduction in Annualized Infection Rate

    Other Secondary Reduction in Annualized Infection Rate End Point Mavorixafor vs Placebo (ITT Population) 8 Annualized infection rate, meanb • 60% reduction in 7 annualized infection 6 rate (P<.01)a 5 • >80% reduction in 4 infection rate with 3 mavorixafor vs placebo 2 during 6-12 months 1 (P<.005)a

11. Slide 11: Types of Infections

    Other Types of Infections Secondary End Point Lower Frequency of Skin, Oral, and Upper and Lower Respiratory Tract Infections Were Observed in the Mavorixafor Group 40 36 35 30 Infections, n 25 25 20 15 14 10 5 5 4 5 2 2 3 2 2 2 0 0 0 1 0 0 0 a URT Skin LRT GI Eyes Ears Urinary Oral Genital tract Ma

12. Slide 12: Duration of Infection

    Other Duration of Infection Secondary End Point Total Time With Infection Was >70% Lower With Mavorixafor vs Placebo • Mean total time with infection: ≈2 weeks on mavorixafor vs ≈7 weeks on placebo • Median total time with infection showed ≈75% reduction with mavorixafor Mavorixafor Placebo Total ti

13. Slide 13: Severity of Infections

    Other Severity of Infections Secondary End Point Less Severe Infections With Mavorixafor Compared With Placebo Over 52 Weeks Participants Experiencing ≥ Grade 3 Infection Severitya 35 30 29 Mavorixafor Placebo Participants, % CTCAE Criteria, n (n=14) (n=17) 25 Grade 1 / Grade 2 10 11 20 Grade 3 1b 4

14. Slide 14: Participants on Placebo More Often Required Treatment With Antibacterials

    Other Participants on Placebo More Often Required Secondary End Point Treatment With Antibacterials Consistent With Higher Rate and Severity of Infections • 10/17 (59%) on placebo were administered antibacterials/penicillins vs 3/14 (21%) on mavorixafor • Amoxicillin or amoxicillin with another anti

15. Slide 15: Evaluation of Warts

    Other Evaluation of Warts Secondary End Point No New Warts Were Observed in Mavorixafor Group for Participants Without Warts at Baseline Baseline New warts over 52 wk 14 12 12 10 Participants, n 10 8 6 6 4 3 2 1 0 0 With warts at baseline With warts at baseline Without warts at baseline Mavorixafor

16. Slide 16: Safety Assessment

    Safety Assessment Mavorixafor Placebo Total • No deaths were reported (n=14) (n=17) (N=31) Subjects, Subjects, Subjects, • No TESAEs were deemed drug System Organ Class Events Events Events n (%) n (%) n (%) related: TESAEs included Any TEAE 14 (100) 88 17 (100) 143 31 (100) 231 infections, glioma,

17. Slide 17: Summary

    Summary • The trial met its primary and first key secondary end points • Mean TATANC for mavorixafor vs placebo was 15.04 vs 2.75 hours (P<.0001), respectively • Mean TATALC for mavorixafor vs placebo was 15.80 vs 4.55 hours (P<.0001), respectively • Compared with the placebo group, mavorixafor grou

18. Slide 18: Acknowledgements

    Acknowledgements • The authors would like to thank the trial participants and their families and caregivers, investigators, and investigational site staff • The authors also acknowledge Diego Cadavid, MD, and Sarah Cohen, MD, formerly of X4 Pharmaceuticals, Inc, Paula Ragan, PhD, Lori Neri, Eloisa C

19. Slide 19: Thank you!

    Thank you! ClinicalTrials.gov Identifier NCT03995108

20. Slide 20: References

    References 1. Heusinkveld LE, et al. J Clin Immunol. 2019;39(6):532-556. 2. WHIM syndrome. National Organization for Rare Disorders. 2020. Accessed May 1, 2023. https://rarediseases.org/rare-diseases/whim-syndrome/ 3. Heusinkveld LE, et al. Expert Opin Orphan Drugs. 2017;5(10):813-825. 4. Bachelerie

X4 Pharmaceuticals — Technical Presentation (May 2023) on 6ix