REGN7999 / Regeneron - LARVOL DELTA

Single Ascending Doses of REGN7999, a Monoclonal Antibody Inhibitor of TMPRSS6, Increase Serum Hepcidin and Cause Deep, Sustained Reductions in Serum Iron in Healthy Human Volunteers (ASH 2023) - P1 | "Single doses of REGN7999 are well tolerated by healthy volunteers and lead to sustained reductions in serum iron with no associated safety concerns. These findings support continued development of REGN7999 for the treatment of IOL."

Clinical • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • KLK7 • TMPRSS6

TMPRSS6 Inhibition Rapidly Reverses Liver Iron Overload and Prevents an Increase of Splenic Pro-Inflammatory Macrophages in a Mouse Model of Beta-Thalassemia (ASH 2024) - "In support of this, we found a significant reduction of Granulocyte/Macrophage-colony-stimulating-factor in the serum of Hbbth3/+ mice treated with REGN7999. Taken together, these data suggest that splenic macrophages are not more pro-inflammatory in response to TMPRSS6 inhibition, despite iron load status."

Preclinical • Anemia • Beta-Thalassemia • Diabetes • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Type 2 Diabetes Mellitus • KLK7 • TMPRSS6

A TMPRSS6-inhibiting mAb improves disease in a β-thalassemia mouse model and reduces iron in healthy humans. (PubMed, JCI Insight) - P1 | "In a phase I, doubleblind, randomized, placebo-controlled study in healthy human volunteers (NCT05481333), REGN7999 increased serum hepcidin and reduced serum iron with an acceptable tolerability profile. Our results suggest that, by both reducing iron and improving RBC function, inhibition of TMPRSS6 by REGN7999 may offer a therapy for iron overload and impaired erythropoiesis in β-thalassemia."

Clinical • Journal • Preclinical • Beta-Thalassemia • Diabetes • Fibrosis • Genetic Disorders • Heart Failure • Hematological Disorders • Immunology • Liver Cirrhosis • Metabolic Disorders • BMP6 • KLK7 • MAD1L1 • SMAD1 • TMPRSS6

EFFICACY, SAFETY, AND TOLERABILITY OF REGN7999 IN PATIENTS WITH IRON OVERLOAD DUE TO NON-TRANSFUSION-DEPENDENT ß-THALASSEMIA: DESIGN OF THE PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED FERVENT-1 TRIAL (EHA 2025) - P2 | "This study will assess the efficacy, safety, and tolerability of REGN7999 in patients with IOL due to non-transfusion-dependent β-thalassemia."

Clinical • P2 data • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • KLK7 • TMPRSS6

FERVENT-1: A Study to Test the Safety, Tolerability, and Efficacy of an Antibody, REGN7999, Injected Under the Skin for the Treatment of Iron Overload in Adult Participants With Non-Transfusion Dependent β-thalassemia, Using MRI Scans to Measure Iron Levels in the Body (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

SINGLE ASCENDING DOSES OF REGN7999, A MONOCLONAL ANTIBODY INHIBITOR OF TMPRSS6, INCREASED SERUM HEPCIDIN AND CAUSED DEEP, SUSTAINED REDUCTIONS IN SERUM IRON IN HEALTHY HUMAN VOLUNTEERS (EHA 2024) - P1 | "Single doses of REGN7999 were well tolerated by healthy volunteers, and led to sustained reductions in serumiron with no associated safety concerns. These findings support the continued development of REGN7999 forthe treatment of IOL."

Clinical • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • KLK7 • TMPRSS6

TMPRSS6 INHIBITION IMPROVES BONE HEALTH IN B-THALASSEMIA MICE (EHA 2024) - "To target the iron overload, we generated a monoclonal antibody (REGN7999) inhibiting TMPRSS6, anegative regulator of hepcidin, the main iron homeostasis regulating hormone... These findings indicate that the reduced bone health is due to reduced boneformation. Taken together, these data suggest that improving red blood cell health and reducing iron loadingreverses the b-thalassemia associated osteoporosis. This effect can potentially improve the quality of life of b-thalassemia patients."

Preclinical • Beta-Thalassemia • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Liver Cirrhosis • Osteoporosis • Rheumatology • TMPRSS6

TMPRSS6 INHIBITION RAPIDLY REVERSES LIVER IRON OVERLOAD AND SPLENOMEGALY IN THALASSEMIC MICE (EHA 2024) - "We have previously shown that inhibition of TMPRSS6 using amonoclonal antibody (REGN7999) reduces serum and liver iron, and improved erythropoiesis leading toreduced splenomegaly in beta-thalassemia mice... Taken together, these data suggest that TMPRSS6 inhibition induces a rapid reversal ofsplenomegaly, which is likely due to improved effectiveness of erythropoiesis. Iron is removed from the liverand this unloading of liver iron becomes evident after the improvement of splenomegaly. The mechanism forthis and the question of what happens to the iron are currently under further investigation."

Preclinical • Anemia • Beta-Thalassemia • Diabetes • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus • KLK7 • TMPRSS6

FERVENT-1: A Study to Test the Safety, Tolerability, and Efficacy of an Antibody, REGN7999, Injected Under the Skin for the Treatment of Iron Overload in Adult Participants With Non-Transfusion Dependent β-thalassemia, Using MRI Scans to Measure Iron Levels in the Body (clinicaltrials.gov) - P2 | N=95 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Beta-Thalassemia • Genetic Disorders • Hematological Disorders