X4 Pharmaceuticals, Inc. · NASDAQ:XFOR

X4 Pharmaceuticals — Technical Presentation (February 2024)

15 slides from X4 Pharmaceuticals's technical presentation, February 2024

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 the Treatment of Participants With WHIM Syndrome: Investigational Assessment of Lymphocyte Subpopulations in Peripheral Blood Raffaele Badolato,1 Teresa K. Tarrant,2 4WHIM Study Group, Yanping Hu,3 Lars Karlsson,4 Halenya Monti

2. Slide 2: Study Group

   Study Group Author Affiliation Author Affiliation Hospital Sant Joan de Déu, Barcelona, Spain; Universitat de Barcelona, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Laia Alsina, MD, PhD Spain; Institut de Recerca Sant Joan de Déu, Barcelona, Spain Sevilla, IBiS/Universidad d

3. Slide 3: Presenting Author Disclosures

   Presenting Author Disclosures Teresa K. Tarrant, MD is a principal investigator in the Phase 3 trial of mavorixafor for WHIM syndrome and consultant to X4 Pharmaceuticals Dr Tarrant has also consulted for the US Department of Justice, has served as an independent grant reviewer for Pfizer, and has r

4. Slide 4: WHIM Syndrome at a Glance

   WHIM Syndrome at a Glance Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) Syndrome, is a rare combined primary immunodeficiency and chronic neutropenic disorder resulting from impaired leukocyte mobilization from bone marrow to peripheral blood. It is characterized by chronic neutrope

5. Slide 5: CXCR4 Antagonism as a Potential Strategy for Treatment of WHIM Syndrome

   CXCR4 Antagonism as a Potential Strategy for Treatment of WHIM Syndrome • CXCR4 is highly expressed on most leukocytes, including all B and most T lymphocytes and their subsets1-4 • CXCR4-CXCL12 signaling regulates the balance between retention of immune cells in the bone marrow and egress to periph

6. Slide 6: Evaluation of Mavorixafor as a Treatment for WHIM Syndrome

   Evaluation of Mavorixafor as a Treatment for WHIM Syndrome Phase 2 trial Increases in peripheral neutrophils, lymphocytes, monocytes, and WBCs were (NCT03005327; PMID: 32870250) observed1,2 Randomized, placebo-controlled, double-blind trial evaluated efficacy and safety Phase 3 trial of once-daily m

7. Slide 7: Key Baseline Laboratory Characteristics

   Key Baseline Laboratory Characteristics Normal range Mavorixafor (n=14) Placebo (n=17) (106/µL)1,2 Value n Value n Blood cell counts, mean (95% CI), 106/La Lymphocytes 485.8 (268.0-703.5) 9 519.9 (300.4-739.4) 15 959-3644 B cellsb 17.8 (1.7-33.9) 9 40.4 (2.1-78.8) 14 106.0-364.6 T cellsb CD4+ T cell

8. Slide 8: Patients Treated With Mavorixafor Showed Increases in Mean ALC From Baseline Over 52 Weeks

   Patients Treated With Mavorixafor Showed Increases in Mean ALC From Baseline Over 52 Weeksa (ITT Populationb) Mean ALC 2200 P<.001a P=.02a LS mean (95% CI), cells/μL P<.001a P<.001a 1800 1400 1000 600 200 -200 Week 0 13 26 39 52 Mavorixafor n: 13 13 11 9 11c Placebo n: 16 16 17 17 17d ALC, absolute

9. Slide 9: Mean Total B Cell and Subpopulation Counts Increased and Were Sustained

   Mean Total B Cell and Subpopulation Counts Increased and Were Sustained 4 Hours After Dose With Mavorixafor vs Placebo Total B Cellsa-d Select B Cell Subpopulationsa,b Predose 4 h after dose Predose 4 h after dose 1500 1500 P<.0001d P<.0001d Mean cell number, 106/L Mean total B cells, 106/L (CD45+CD

10. Slide 10: Mean Total CD4+ T Cell and Subpopulation Counts Increased and Were Sustained

    Mean Total CD4+ T Cell and Subpopulation Counts Increased and Were Sustained 4 Hours After Dose With Mavorixafor vs Placebo Total CD4+ T Cellsa-d Select CD4+ T Cell Subpopulationsa,b Predose 4 h after dose Predose 4 h after dose 2000 P<.0001d 2000 P<.0001d P<.0001d P<.0001d Mean total CD4+ T cells,

11. Slide 11: Mean Total CD8+ T Cell and Subpopulation Counts Increased and Were Sustained

    Mean Total CD8+ T Cell and Subpopulation Counts Increased and Were Sustained 4 Hours After Dose With Mavorixafor vs Placebo Total CD8+ T Cellsa-d Select CD8+ T Cell Subpopulationsa,b Predose 4 h after dose Predose 4 h after dose 1000 1000 Mean total CD8+ T cells, 106/L P<.0001d Mean cell number, 106

12. Slide 12: Mean Total NK Cell Counts Were Unchanged With Mavorixafor and Similar to Placebo

    Mean Total NK Cell Counts Were Unchanged With Mavorixafor and Similar to Placebo Predose 4 h postdose 500 ULNd (CD45+CD3-CD16+ CD56+)a-c Mean total NK cells, 106/L 400 300 200 ns ns ns ns ns 100 LLNd 0 Week 0 0 13 26 39 52 Mavorixafor n: 9 9 11 10 9 6e Placebo n: 14 13 11 15 14 14f ANOVA, analysis o

13. Slide 13: Mavorixafor Normalizes Absolute B- and T-Cell Counts Without Prolonging Elevation at Trough

    Mavorixafor Normalizes Absolute B- and T-Cell Counts Without Prolonging Elevation at Trough Total B Cells Counta,b Total CD4+ T Cells Counta,b Total CD8+ T Cells Counta,b Mean total CD4+ T cells, 106/L Mean total CD8+ T cells, 106/L 1500 2000 1000 Mean total B cells, 106/L 800 1500 1000 ULNc ULNc 60

14. Slide 14: Conclusions

    Conclusions • Statistically significant increases in peripheral blood lymphocyte counts were observed in mavorixafor-treated participants compared with placebo: B cells CD4+ T cells and CD8+ T cells ↑ Switched memory, ↑ unswitched memory, ↑ Central memory, ↑ effector memory, and ↑ naïve and ↑ naïve

15. Slide 15: 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 Andrea Belschner, CCRP; Atil Bisgin, MD; Diego Cadavid, MD; Eloisa Chapa, MPH; Kelly Chen, PhD; Sarah Cohen, MD; E

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