X4 Pharmaceuticals, Inc. · NASDAQ:XFOR
X4 Pharmaceuticals — Technical Presentation (May 2023)
23 slides from X4 Pharmaceuticals's technical presentation, May 2023
Slide 1: Results of a Phase 3 Trial of an Oral CXCR4 Antagonist, Mavorixafor, for WHIM Syndrome
Results of a Phase 3 Trial of an Oral CXCR4 Antagonist, Mavorixafor, for Treatment of Patients With WHIM Syndrome ClinicalTrials.gov Identifier NCT03995108 1
Slide 2: 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
Slide 3: 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
Slide 4: 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
Slide 5: 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
Slide 6: 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
Slide 7: 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
Slide 8: 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
Slide 9: 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
Slide 10: 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
Slide 11: 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
Slide 12: 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
Slide 13: 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
Slide 14: 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
Slide 15: 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,
Slide 16: 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
Slide 17: 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
Slide 18: Thank you!
Thank you! ClinicalTrials.gov Identifier NCT03995108
Slide 19: 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
Slide 20: Backup slides
Backup slides ClinicalTrials.gov Identifier NCT03995108 20
Slide 21: Genetic Variants in the Trial Population
Genetic Variants in the Trial Population Genetic variant, n (%) Mavorixafor Placebo (n=14) (n=17) c.1000C>T p.Arg334* 10 (71.4) 12 (70.6) c.1013C>G p.Ser338*3 1 (7.1) 2 (11.8) c.950_953del p.Leu317Profs*3 1 (7.1) 1 (5.9) c.959_960del p.Val320Glufs*23 1 (7.1) 1 (5.9) c.976dup p.Leu326Profs*18 1 (7.1)
Slide 22: Summary of AEs
Summary of AEs Mavorixafor Placebo Mavorixafor Placebo Mavorixafor Placebo (n=14) (n=17) (n=14) (n=17) (n=14) (n=17) Any TEAE, n (%) 14 (100.0) 17 (100) TEAEs reported in ≥2 Any Grade ≥3 Any grade Grade ≥3 Treatment-related Any grade Grade ≥3 Any grade Grade ≥3 participants in either grade TEAEsa, n
Slide 23: WHIM Syndrome Biomarker Summary
Other Secondary End Point WHIM Syndrome Biomarker Summary • Considerable increases in WBC, ANC, ALC, and AMC levels were observed in the mavorixafor group compared with placebo group • When compared to baseline: • ALC and AMC levels increased into the normal range in the mavorixafor group • WBC and
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