Slide 1: Chronic Neutropenia: Mavorixafor Beyond WHIM Syndrome
Chronic Neutropenia Mavorixafor Beyond WHIM Syndrome September 27, 2022 Exhibit 99.2
Slide 2: Forward-Looking Statements
2 Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “inten
Slide 3: Event Outline
Event Outline 01 02 03 04 05 06 Welcome Overview of Chronic Neutropenia Insights into Current Treatment Paradigm Phase 1b Clinical Trial Objectives and Results Future Potential of Mavorixafor in CN Disorders Conclusion and Q&A
Slide 4: Chronic Neutropenia: a Severe Condition with Significant Unmet Needs
4X4 Pharmaceuticals Overview | Company Confidential Chronic Neutropenia (CN): a Severe Condition with Significant Unmet Needs Image source: “Understanding Severe Chronic Neutropenia: A handbook for patients and their families,” SCNIR 2017; Table data and information on infection risk: https://neutro
Slide 5: CXCR4 Plays a Key Role in Maturation & Mobilization of Neutrophils
5 CXCR4 Plays A Key Role in Maturation & Mobilization of Neutrophils 1. Bainton DF (1980) The cells of inflammation: a general view. In Weissmann G (ed) The Cell Biology of Inflammation, vol 2, pp 1–25. Amsterdam: Elsevier/North-Holland 2. Furze RC, et al, Immunology. 2008 3. Kim HK, et al, Blood. 2
Slide 6: Mavorixafor: the only oral CXCR4 antagonist in development
6 Mavorixafor Mavorixafor: the only oral CXCR4 antagonist in development • A small molecule with high potency and selectivity • Demonstrated ability to increase the mobilization of white blood cells, including neutrophils, from bone marrow to bloodstream • Durable half-life supporting once-daily dos
Slide 7: Injectable G-CSF is the Only Approved Therapy for CN Disorders
Injectable G-CSF is the Only Approved Therapy for CN Disorders Injections of G-CSF • Approved for idiopathic, cyclic, and congenital severe CN • Up to twice-daily to increase neutrophil counts and reduce severe neutropenia, infection risk • Recommended starting dose 5-6 mcg/kg twice daily • Often do
Slide 8: Significant Challenges with G-CSF: 100-Patient Survey Results
8 100-Patient Survey1 Results: 1. August 2022 Savvy Cooperative Survey Results: Neutropenia Patient Perspective Significant Challenges with G-CSF 91 experienced with G-CSF • 51 surveyed could tolerate continuing G-CSF treatment: • 76% (39) of them noted bone pain as a side effect • 75% (38) patients
Slide 9: Significant Potential Across CN Disorders Studied in Phase 1b Trial
9 Significant Potential Across CN Disorders Studied in Phase 1b Trial 1. U.S. Prevalence Based on ICD-10 Code Research, Average Across 3 Years (2018, 2019, & 2021); >90% greater than 18 years of age, ~2/3 female, mixed G-CSF use ~50,000 Estimated Chronic Neutropenia Patients in the U.S.1 Idiopathic
Slide 10: Objectives of X4's Phase 1b Study in Chronic Neutropenic Disorders
10 Objectives of X4’s Phase 1b Study in Chronic Neutropenic Disorders PRIMARY STUDY OBJECTIVES Assess mavorixafor treatment for safety and ability to increase absolute neutrophil count (ANC) across a range of chronic neutropenic disorders (idiopathic, cyclic, congenital) Three Exploratory Sub-Analys
Slide 11: Measuring Maximum ANC Increase After Single Oral Dose of Mavorixafor
11 Measuring Maximum ANC Increase After Single Oral Dose of Mavorixafor MAVORIXAFOR IMPACT Day 1 BASELINE Day -1 Time (Hours) A N C ANC Over Time Peak absolute change in ANC vs. baseline Trial Design Trial Measurements Baseline value defined as average ANC over Day-1
Slide 12: Phase 1b CN Trial Demographics & Safety Summary
12 Phase 1b CN Trial Demographics & Safety Summary Overall Idiopathic Congenital Cyclic # Patients 25 16 6 3 Mean Age 36 37 32 41 Male/Female 10/15 6/10 1/5 3/0 On/Off G-CSF 18/7 10/6 5/1 3/0 Baseline G-CSF Dose for Those Treated Median (mcg/kg/day)* 1.09 0.56 1.09 1.09 Phase 1b Trial in CN Disorder
Slide 13: Primary Objective: 100% of Patients Responded
13 Primary Objective: 100% of Patients Responded • All participants responded • Suggests bone marrow reserve of neutrophils can be accessed • Responses exceeded 500 cells/µL for every individual participant Increase in ANC (D ANC) Post-Mavorixafor Dose Individual participants (N=25) P e a k I n c re
Slide 14: Oral Mavorixafor Increased ANC By >3,000 cells/µL
14 Primary Objective Results: Oral Mavorixafor Increased ANC By >3,000 cells/µL Consistent, large increases seen across all CN disorders studied (idiopathic, congenital, cyclic) 0 1 2 3 4 5 6 7 8 9 10 Idiopathic (N=16) Congenital (N=6) Cyclic (N=3) Pre- and Post-Mavorixafor ANC Levels Across CN Diso
Slide 15: Participants: Sub-Groups
15 25 Participants: 3 Sub-Groups (no overlap between groups) N = 6 N = 8 N = 11* Assess impact of mavorixafor monotherapy in neutropenic patients Severe Neutropenia at Screening Mean ANC = 420 cells/µL No G-CSF Exploratory Sub-Analyses: Patient Numbers and Baseline Profiles Assess impact of mavorixa
Slide 16: Sub-Analysis 1: Mavorixafor Monotherapy Normalized ANC
16 Sub-Analysis 1: Mavorixafor Monotherapy Normalized ANC in Neutropenic Patients Kinetics and Mean Increase in ANC 0 0.5 1 1.5 2 2.5 3 3.5 4 Subjects Not Treated with G-CSF (N=6) Baseline Post-Mav Treatment Severe Neutropenia Minimum “Normal” ANC Mean Peak ANC M e a n P e a k A N C ( 1 0 0 0 c e ll
Slide 17: Sub-Analysis 1: Individual Participant Data
17 Sub-Analysis 1: Mavorixafor Monotherapy Normalized ANC in Neutropenic Participants Individual Participant Data All patients had severe neutropenia pre-treatment Severe Neutropenia Minimum “Normal” ANCA N C ( 1 0 0 0 c e ll s /µ L ) • All (100%) participants responded • All (100%) achieved normali
Slide 18: Sub-Analysis 2: Mavorixafor + G-CSF Normalized ANC
18 Sub-Analysis 2: Mavorixafor + G-CSF Normalized ANC in Neutropenic Participants • ANC reached normal levels throughout dosing cycle • Mean ANC increase of >3,000 cells/µL in neutropenic patients Kinetics and Mean Increase in ANC 0 1 2 3 4 5 6 On G-CSF (N=8) Baseline Post-Mav Treatment Minimum “Nor
Slide 19: Sub-Analysis 2: Individual Participant Data
19 c Sub-Analysis 2: Mavorixafor + G-CSF Normalized ANC in Neutropenic Participants Individual Participant Data All are neutropenic; 5/8 (~60%) participants continued to have moderate or severe neutropenia although on G-CSF A N C ( 1 0 0 0 c e ll s /µ L ) • All (100%) participants responded • All (1
Slide 20: Sub-Analysis 3: Mavorixafor + G-CSF Increased ANC in Non-Neutropenic Participants
20 cc Sub-Analysis 3: Mavorixafor + G-CSF Increased ANC in Non-Neutropenic Participants To Assess Potential for G-CSF Taper: Kinetics and Mean Increase in ANC 0 2 4 6 8 10 12 On G-CSF (N=11) Baseline Post-Mav Treatment Further supports exploring potential of mavorixafor to reduce use of G-CSF M e a
Slide 21: Study Conclusions: Favorable Results Support Path Forward in CN
21 Study Conclusions: Favorable Results Support Path Forward in CN Primary Objectives Met All Participants Responded • All CN Disorders – Idiopathic, Cyclic and Congenital – responded to mavorixafor • Increase in ANC of >2,000 cells/µL across all disorders Potential for Mavorixafor Monotherapy • Mav
Slide 22: Potential New, Oral Treatment for Chronic Neutropenic Disorders, including WHIM
22 Potential New, Oral Treatment for Chronic Neutropenic Disorders, including WHIM 1. Dale, Blood, 2019. 2. Dale, ASH, 2021. 3. X4 WM = Waldenstrom’s Macroglobulinemia; Data released in X4 Q3 Earnings Presentation, August 2022. ANC elevations and corresponding reduction in infection burden being ass
Slide 23: Significant Near-Term Milestones / Meaningful Growth Potential
23 Significant Near-Term Milestones / Meaningful Growth Potential 1. Phase 1b protocol amendment near completion: 6-month dosing in up to 50 patients to assess ANC durability, G-CSF taper, tolerability vs. G-CSF and other. 4WHIM Phase 3 Trial Readout Amended1 Phase 1b CN Protocol Initiation Phase 1b
Slide 24: Sharp focus on chronic neutropenic disorders
24 Sharp focus on chronic neutropenic disorders Unparalleled expertise in immune system dysfunction and CXCR4 biology Mavorixafor – a late-stage clinical CXCR4 antagonist candidate with broad commercial potential Key mavorixafor clinical milestones expected over next 3 to 6 months Strong balance she