Neurogene Inc. · NASDAQ:NGNE
Neurogene — 2025 ASGCT Meeting
10 slides from Neurogene's conference presentation, May 16, 2025
Slide 1: Hemophagocytic Lymphohistiocytosis (HLH)/Hyperinflammatory Syndrome Following High Dose AAV9 Therapy
Hemophagocytic Lymphohistiocytosis (HLH)/ Hyperinflammatory Syndrome Following High Dose AAV9 Therapy Aimee Donald, MBChB, PhD 2025 ASGCT Meeting 16 May 2025 Aimee Donald1, Simon Jones1, Barry J. Byrne2, Randy Q. Cron3, Cynthia Feng4, Effie Albanis4, Francesco Bibbiani4, Stuart Cobb4, Julie Jordan4
Slide 2: Disclosures
Disclosures Travel honoraria with Neurogene Consultant: Sanofi, Prevail (Lilly), Avrobio Investigator with: Sanofi, Neurogene, Takeda, Denali, Intrabio, UCB, Moderna 2
Slide 3: Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytic Lymphohistiocytosis (HLH) • HLH is a rare, life-threatening hyperinflammatory syndrome characterized by immune dysregulation, cytokine storm, and multi-organ damage1-3 • Most cases are triggered by infections, malignancy, autoimmune disease, or CAR- T (3.5% incidence) • Over 90% of pa
Slide 4: HLH has been Rarely Reported Following High-dose AAV Gene Therapy
HLH has been Rarely Reported Following High-dose AAV Gene Therapy • Only one published case report1 and mention of similar cases2 reported HLH-like symptoms with high-dose systemic AAV treatment (1E14 vg/kg or higher) • Symptoms: Elevated ferritin within the first few days, fever, pancytopenia, rash
Slide 5: Case Presentation: HLH/Hyperinflammatory Syndrome in AAV Study
Case Presentation: HLH/Hyperinflammatory Syndrome in AAV Study • Participant in RTT-200 trial: Participant with classic Rett syndrome; received 3E15 total vg (1.5E14 vg/kg)1 of NGN-401 • Prophylactic immunomodulation: Steroids/sirolimus/rituximab • Two other participants had been treated with the 3E
Slide 6: HLH Suspected and Maximal Care Provided
HLH Suspected and Maximal Care Provided Ferritin level 18,850 ug/L (normal <150 ug/L) At re-admission: Diagnosed with dehydration; started on IV fluids and oxygen Treatment: Antibiotics, high-dose hydrocortisone Labs: Thrombocytopenia, elevated liver enzymes and LDH, coagulopathy Rapid clinical decl
Slide 7: FAERS Database Shows HLH/HLH-Like Symptoms Following High-Dose Systemic AAV (>1E14 vg/kg)
FAERS Database Shows HLH/HLH-Like Symptoms Following High- Dose Systemic AAV (>1E14 vg/kg) While HLH is extremely rare, emerging post-marketing data suggests that HLH-like immune responses may occur in a small subset of patients treated with high-dose systemic AAV gene therapy1 • HLH-Related Finding
Slide 8: HLH Risk Mitigation Strategy Should be Implemented for AAV Gene Therapy
HLH Risk Mitigation Strategy Should be Implemented for AAV Gene Therapy • Dose level above 1E14 vg/kg not allowed • In the first week post dosing: employ daily monitoring of ferritin, fever, and falling blood counts (cytopenia) • Exclude subjects with: Risk Mitigation • Any illness within 30 days of
Slide 9: Key Conclusions: HLH can be Reversed if Recognized Early
Key Conclusions: HLH can be Reversed if Recognized Early • HLH is rarely described but has occurred in the setting of high-dose AAV therapy • Key early signs and symptoms include fever, elevated ferritin, and falling blood counts (cytopenias) - Fever within the first few days post-dosing warrants fu
Slide 10: Thank You, and Acknowledgments
Thank You, and Acknowledgments • Families • Neurogene team and co-investigators • HLH and gene therapy experts who consulted on this case 10