X4 Pharmaceuticals, Inc. · NASDAQ:XFOR
X4 Pharmaceuticals — Investor Day (May 2023)
29 slides from X4 Pharmaceuticals's investor day presentation, May 16, 2023
Slide 1: A Deeper Dive into Mavorixafor Phase 3 Data and Unmet Patient Needs in WHIM Syndrome
PROGRESS PATIENTS A Deeper Dive into Mavorixafor Phase 3 Data and Unmet Patient Needs in WHIM Syndrome May 16, 2023
Slide 2: Forward-Looking Statements
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,” “intend,
Slide 3: Today’s Agenda
Today’s Agenda 01 Welcome 02 Overview of Mavorixafor Opportunity 03 The Challenge of Infections in WHIM 04 New Phase 3 Data in WHIM 05 Path Forward: WHIM, CN Disorders, and Beyond 06 Conclusion and Q&A
Slide 4: Today’s Event Participants
Today’s Event Participants c c c c c Charlotte Cunningham- Jean Donadieu, MD, PhD Peter Newburger, MD Akiko Shimamura, MD, PhD Teresa Tarrant, MD, FAAAAI Rundles, MD, PhD Pediatric Heme-Oncology, Professor of Pediatrics at Assoc. Professor at Duke Professor of Pediatrics, Professor of Pediatric Chro
Slide 5: Mavorixafor: Potential Breakthrough for Treating Chronic Neutropenic Disorders
Mavorixafor: Potential Breakthrough for Treating Chronic Neutropenic Disorders Only oral candidate in development to treat CN disorders, including WHIM syndrome ✓ Proven mechanism of action (MOA) / ability to increase white blood cells, including neutrophils ✓ Demonstrated tolerability in >200 indiv
Slide 6: Mavorixafor’s Market Potential: Addressing Infection Risk in CN and Beyond
Mavorixafor’s Market Potential: Addressing Infection Risk in CN and Beyond Chronic Neutropenic (CN) Disorders ~50,000 CN Patients in US • Increased risk of serious infections at increased risk of infections • Neutropenia • ~50,000 estimated US patients1 Chronic Neutropenic idiopathic Disorders WHIM
Slide 7: WHIM Syndrome: Poorly Functioning Immune System, Starting from Birth
WHIM1 Syndrome: Poorly Functioning Immune System, Starting from Birth Increased Risk of Infections Clinical diagnosis driven by over-signaling in the Ear, Sinus, and Lung: Heart: CXCL12/CXCR4 pathway Upper/Lower Endocarditis Respiratory Tract Infections WHIM Disease Bone Marrow2 Decreased white Geni
Slide 8: Infection Risk Tracks with Neutropenia in WHIM Syndrome
Infection Risk Tracks with Relationship Between Neutropenia & Infections in Neutropenia in WHIM Syndrome WHIM Syndrome Natural History • Infections start within the first year of life • Neutropenia tracks with infection risk from birth and continues as patients age • Most patients have both neutrope
Slide 9: 4WHIM Pivotal Phase 3 Clinical Trial Overview
4WHIM Pivotal Phase 3 Clinical Trial Overview Primary Endpoint Assessed Mavorixafor (N= 14) Screening 1: 1 ~90% Rolled Over into Randomization Baseline Open-Label Extension (OLE) Visit Placebo (N = 17) Baselines: 100% of patients had severe chronic neutropenia (median ANC ~200 cells/mL) and chronic
Slide 10: Mavorixafor Phase 3 Clinical Trial Results Summary
Phase 3 Clinical Trial Reduced Reduced Reduced Mavorixafor RATE SEVERITY DURATION demonstrated of infections of infections of infections significant clinical benefit & favorable safety profile 4WHIM trial met primary endpoint of time above threshold for absolute neutrophil counts (TATANC) and key cl
Slide 11: Mavorixafor MOA Proven
Mavorixafor MOA Proven Statistically Significant Increases in Total White Blood Cell (WBC) and Absolute Neutrophil Counts (ANC) over the 52 Week Study Increased Cell Counts Lower limit of normal for white blood cell counts LS Mean +/- • Statistically significant, durable Total WBC Count 1 95% CI inc
Slide 12: Infections Are The Major Problem in WHIM: Mavorixafor Delivered Benefit
Phase 3 Clinical Trial Reduced Reduced Reduced RATE SEVERITY DURATION of infections of infections of infections Infections Are The Major Problem in WHIM: Mavorixafor Delivered Benefit 12
Slide 13: Statistically Significant 58% Reduction in Annualized Infection Rate
Statistically Significant 58% Reduction in Annualized Infection Rate Mavorixafor versus placebo (ITT population) Annualized Infection Rate 6 Mavorixafor 5 Placebo P value <0.01 Infections Per Year 4 3 ~60% reduction 2 1 0 13
Slide 14: Deeper Reductions in Infection Rate with Time on Mavorixafor Treatment
Deeper Reductions in Infection Rate with Time on Mavorixafor Treatment First 6-months vs. second 6-months (ITT population) Annualized Infection Rate by 6-month Interval (mean ± 95% CI) 8 7 Annualized Infection Rate (~4.5/year) remained unchanged on placebo 6 Infections/year 5 4 Deeper reductions in
Slide 15: Mavorixafor Reduced Infection Rate Consistently Across Subgroups
Mavorixafor Reduced Infection Rate Consistently Across Subgroups Treatment Difference in Infection Rate (ratio of mavorixafor over placebo) All Sub-Groups Had Benefit Favoring Mavorixafor Treatment ✓ In those with or without concomitant Ig treatment ✓ In both adolescents and adults ✓ In both women a
Slide 16: Mavorixafor Reduced Infections Across Most Organ Systems
Mavorixafor Reduced Infections Across Most Organ Systems Assessment of Warts Reported Benefit Observed in Bacterial, Viral, and Fungal Infections First placebo-controlled study assessing warts in WHIM ~60% Mavorixafor Placebo • ~70% of patients had warts reduction • Warts assessed at wks 0, 26, ~90%
Slide 17: Infections are the Major Problem in WHIM: Mavorixafor Delivered Benefit
Phase 3 Clinical Trial Reduced Reduced Reduced RATE SEVERITY DURATION of infections of infections of infections Infections are the Major Problem in WHIM: Mavorixafor Delivered Benefit 17
Slide 18: Severity of Infections: Assessed by Standard CTCAE Criteria
Severity of Infections: Assessed by Standard CTCAE1 Criteria • Severe Infections: Grade 3 or Higher • Require significant intervention (oral and/or IV antibiotics) and/or hospitalization • Assessed by blinded, centralized, independent, adjudication committee Severity Scale Description Grade 3 Severe
Slide 19: More Patients on Placebo Experienced Severe Infections Over 52 Weeks
More Patients on Placebo Experienced Severe1 Infections Over 52 Weeks Percentage of Patients Experiencing Grade 3 or Higher Infection Severity Mavorixafor Placebo 35% (n=14) (n=17) CTCAE Criteria N N 30% 29% Grade 1 / Grade 2 10 11 25% Grade 3 1* 4 % OF PATIENTS 20% Grade 4 0 1 15% Grade 5 0 0 *Grad
Slide 20: Patients on Placebo More Heavily Treated with Anti-bacterials
Patients on Placebo More Heavily Treated with Anti-bacterials Consistent with higher rate and severity of infections • 10/17 (59%) on placebo were administered anti-bacterials/penicillins vs. 3/14 (21%) on mavorixafor • Amoxicillin or amoxicillin+other combination were most commonly prescribed anti-
Slide 21: Infections are the Major Problem in WHIM: Mavorixafor Delivered Benefit
Phase 3 Clinical Trial Reduced Reduced Reduced RATE SEVERITY DURATION of infections of infections of infections Infections are the Major Problem in WHIM: Mavorixafor Delivered Benefit 21
Slide 22: Total Time with Infection Reduced by >70% with Mavorixafor vs. Placebo
Total Time with Infection Reduced by >70% with Mavorixafor vs. Placebo • Mean total time with infection: ~2 weeks on mavorixafor vs. ~7 weeks on placebo • Median total time with infection also showed (~75%) reduction Total Time with Infection (in days) Mavorixafor Placebo (n=14) (n=17) Mean (SD) 14.
Slide 23: Oral Mavorixafor was Well Tolerated in the Trial
Oral Mavorixafor was Well Tolerated in the Trial Top-line safety data summary for randomization period Overall • No treatment-related Serious Adverse Events (SAEs) • No treatment-limiting toxicities • No discontinuations due to safety events • ~90% of patients continued into the Open Label Extension
Slide 24: Safety Assessment: Supports Chronic Dosing for Mavorixafor
Safety Assessment: Supports Chronic Dosing for Mavorixafor • Placebo arm had increased (3x to 4x) infections/infestations and respiratory disorders • Mavorixafor arm had increased skin & GI disorders • No discontinuations - all were mild, all resolved • Other safety assessments showed balance betwee
Slide 25: Path Forward: Preparing for our First NDA Regulatory Submission
Path Forward: Preparing for our First NDA Regulatory Submission ✓Pre-NDA meeting with FDA completed in early Q2 • WHIM Phase 3 clinical and other data discussed X4 Eligible for ✓Overall favorable commentary and guidance Priority Review US NDA submission for mavorixafor in the Voucher (PRV) treatment
Slide 26: Preparation Underway for Potential 1H 2024 US Launch in WHIM Syndrome
1 Building the WHIM Syndrome Community • Establish X4 as a trusted partner with key stakeholders Preparation • Educate on WHIM syndrome, highlighting unmet need and Underway for enabling better patient identification Potential 1H 2024 • Support earlier diagnoses leading to better patient outcomes US
Slide 27: Leveraging Our Success in WHIM into Chronic Neutropenic Disorders
Leveraging Our Success in WHIM into Chronic Neutropenic Disorders WHIM Phase 3: Provides Proof of Concept Supporting CN Increased Absolute Neutrophil Counts (ANC) Mavorixafor and Clinical Benefit in Reducing Infection Burden Potential oral, well tolerated, once-daily option for CN Exploring use in i
Slide 28: Maximizing Mavorixafor Potential to Address Infection Risk in CN and Beyond
Maximizing Mavorixafor Potential to Address Infection Risk in CN and Beyond Significant Infection Benefit Shown WHIM Disease Additional PIs On track for US NDA submission >1,000 est. US Patients >250,000 PI patients at early 2H 2023 increased risk of infections in the US1 Phase 2 CN trial data and C
Slide 29: Thank You!
Thank You! — a Sie — a 3 ATNASNG 7 5 ; / y \\ = , | = | F a if = ‘' i" | 4 f | E S : Ui a 7 = [ | i | f | | | ba | | | Fa | SSeS 00 Uo000EReEo0m {EA Been iso =