Slide 1: Mavorixafor for Patients With Chronic Neutropenic Disorders: Results From a Phase 1b Study
Mavorixafor for Patients With Chronic Neutropenic Disorders: Results From a Phase 1b, Open-Label, Multicenter Study Julia T. Warren, MD, PhD1,*; Kelly Walkovich, MD2,*; Audrey Anna Bolyard, RN, BS3; Kathryn E. Dickerson, MD, MS4; Jolan E. Walter, MD, PhD5-7; Diego Cadavid, MD8; Eloisa Chapa, MPH8; K
Slide 2: Mavorixafor is an investigational product
Mavorixafor is an investigational product and the safety and efficacy have not been established. The investigational uses presented here have not been filed with or approved by the FDA or other regulatory authority. FDA, US Food and Drug Administration.
Slide 3: Chronic Neutropenic Disorders
Chronic Neutropenic Disorders Chronic neutropenia Blood disorders characterized by low levels of neutrophils (ANC <1500/µl for >3 months)1,2 Causes of chronic neutropenia CN Disorders Characterized by • Injectable G-CSF is the only approved Persistent neutropenia of unknown therapy for severe chroni
Slide 4: Mavorixafor Is an Oral CXCR4 Antagonist Being Evaluated in Clinical Trials
Mavorixafor Is an Oral CXCR4 Antagonist Being Evaluated in Clinical Trials for Chronic Neutropenic Disorders High potency and selectivity12 Once-daily oral dosing12 Increases peripheral neutrophil count in a phase 2 trial of participants with WHIM syndrome12,13 Mavorixafor antagonizes CXCL12/CXCR4 l
Slide 5: Phase 1b open-label multicenter trial (NCT04154488) overview
Here, we report the findings of phase 1b, open-label, multicenter trial (NCT04154488) evaluating the safety, tolerability, and proof of concept for efficacy, of mavorixafor alone or with concurrent G-CSF use across several CN disorders14,a CN, chronic neutropenic; G-CSF, granulocyte colony–stimulati
Slide 6: A Phase 1b Trial Evaluating Safety and Tolerability of Mavorixafor
A Phase 1b Trial Evaluating Safety and Tolerability of Mavorixafor in Chronic Neutropenic Disorders Trial Design Key Eligibility Criteria Screening • Aged ≥12 years Day ─1 (baselinea) • Diagnosed with CIN, Stable G-CSF dose congenital, or cyclic (if used at baseline) • Multiple ANC assessments were
Slide 7: Phase 1b Trial: Endpoints and Assessments (cont'd)
A Phase 1b Trial Evaluating Safety and Tolerability of Mavorixafor in Chronic Neutropenic Disorders (cont’d) Endpoints and Assessments Primary endpoints • Change and fold change from Day ─1 in ANC levels over 6–8 hours on Day 1 • Incidence and severity of TEAEs Subgroup analyses • Mean change and pe
Slide 8: Fold Change in ANC Levels After Single Dose of Mavorixafor
Primary endpoint Fold Change in ANC Levels After Single Dose of Mavorixafor Change in ANC Levels by Type of CN Disorders (N=25)a,b Change in ANC Levels by G-CSF Use (N=25)a,b 6 8 from Day ─1 to Day 1, mean 7 from Day ─1 to Day 1, mean 5 Average fold change 6 Average fold change 4 5 3 4 3 2 2 No fold
Slide 9: Absolute ANC Change for Participants Not on G-CSF
Subgroup analysis Absolute ANC Change for Participants Not on G-CSFa Mean ANC (n=7)b Mean Peak ANC (n=7)b 4.0 4.0 3.5 3.5 Mean peak ANC, 103 cells/µL Mean ANC, 103 cells/µL 3.0 3.0 2.5 2.5 2.0 2.0 “Normal” ANC “Normal” ANC 1.5 1.5 1.0 1.0 Severe Severe neutropenia neutropenia 0.5 0.5 0.0 0.0 0 1 2 3
Slide 10: Absolute ANC Change for Participants on G-CSF
Subgroup analysis Absolute ANC Change for Participants on G-CSF (Dosed in the Morning) Mean ANC (n=9)a,b Mean Peak ANC (n=9)a,b 12.5 14.0 12.0 Mean peak ANC, 103 cells/µL Mean ANC, 103 cells/µL 10.0 10.0 7.5 8.0 6.0 5.0 4.0 2.0 2.5 0.0 0 2 4 6 8 G-CSF alone Mavorixafor + G-CSF Time after dose, h (Da
Slide 11: Safety Summary
Primary endpoint Safety Summary TEAEs (N=65)a,b Mavorixafor-Related TEAEs (N=51)c AE Toxicity Grade Events, n (%) AE Count, AE Termsb n (%) 1 53 (81.5) CTCAE Grade 1 42 (82.4) 2 11 (16.9) Diarrhea 6 (14.3) 3 1 (1.5) Fatigue 3 (7.1) Functional dyspepsia Data rounded up to 1 decimal place. 3 (7.1) fro
Slide 12: Conclusions
Conclusions • Observe a meaningful increase in ANC after treatment with a single dose of mavorixafor • Responses were seen across the types of CN disorders and G-CSF use • Mavorixafor was overall well tolerated • Our findings support further exploration of mavorixafor in treatment of CN disorders be
Slide 13: Phase 1b trial expanded to up to 25 additional participants
Based on these encouraging early efficacy results, the phase 1b trial has been expanded to evaluate up to 25 additional participants with longer treatment duration (6 months). For more information, please see https://clinicaltrials.gov/ct2/show/NCT04154488 Contact: clinicaltrialinfo@x4pharma.com CN,
Slide 14: Acknowledgements
Acknowledgements The authors would like to thank everyone involved in the clinical development of mavorixafor, including participants enrolled in the clinical trial, families of the participants, the staff at the investigator sites, the clinical research organization, and other vendors. They would a
Slide 15: Questions?
Questions? For full clinical trial details, visit ClinicalTrials.gov identifier: NCT04154488. https://clinicaltrials.gov/ct2/show/NCT04154488
Slide 16: References
References 1. Newburger PE, Dale DC. Semin Hematol. 2013;50(3):198-206. 2. Dale DC, et al. Blood. 1993;81(10):2496-2502. 3. Dale DC, Bolyard AA. Curr Opin Hematol. 2017;24(1):46-53. 4. Skokowa J, et al. Nat Rev Dis Primers. 2017;3:17032. 5. Donadieu J, et al. Expert Rev Hematol. 2021;14(10):945-960.