Rallybio Corporation (NASDAQ: RLYB) has announced the dosing of the first participant in its Phase 2 clinical trial of RLYB212, a monoclonal antibody being developed for the prevention of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT). The trial aims to evaluate the pharmacokinetics (PK) and safety of RLYB212 in pregnant women at increased risk of HPA-1a alloimmunization and FNAIT.
The Phase 2 trial (2024-512651-20/NCT06435845) is a single-arm, dose-confirmation study designed to assess the PK and safety of RLYB212 when administered subcutaneously every four weeks from gestational week 16 through delivery. Secondary objectives include evaluating pregnancy and neonatal outcomes, as well as monitoring for the occurrence of emergent HPA-1a alloimmunization. The trial will enroll participants in three stages: a sentinel pregnant woman, an initial cohort of three pregnant women, and a second cohort of four pregnant women, for a total target enrollment of eight participants. Data review for participants and infants is planned prior to the initiation of each cohort. The trial is being conducted at sites in Europe.
Model-Informed Dosing
Rallybio utilized a target-mediated drug disposition (TMDD) model to inform the dosing regimen for RLYB212. This model accounts for physiological changes during pregnancy and the pharmacodynamics of HPA-1a-positive platelet elimination, as detailed in a manuscript published in Clinical Pharmacology and Therapeutics: Pharmacometrics & Systems Pharmacology.
FNAIT: A Rare and Severe Condition
FNAIT is a rare, potentially life-threatening condition that occurs when a mother develops antibodies against fetal platelets due to an incompatibility in the human platelet antigen 1 (HPA-1). Specifically, HPA-1a-negative mothers carrying HPA-1a-positive fetuses can develop anti-HPA-1a antibodies. These antibodies cross the placenta, leading to the destruction of fetal platelets, which can result in thrombocytopenia and severe complications such as miscarriage, stillbirth, neurological disability, or death of the newborn. There is currently no approved therapy for the prevention or prenatal treatment of FNAIT.
Executive Commentary
Stephen Uden, M.D., Chief Executive Officer of Rallybio, stated, "Dosing the sentinel participant in our RLYB212 Phase 2 trial marks a significant milestone for our RLYB212 program and for Rallybio. In addition to the assessment of safety, we are looking for the PK profile in the sentinel participant to demonstrate the ability of RLYB212 to achieve and maintain target concentrations throughout pregnancy. We plan to provide an update in the second quarter, as we continue to advance our mission to deliver a safe and effective therapeutic to prevent maternal alloimmunization and the potentially catastrophic consequences of FNAIT."
Anticipated Data Readouts
Preliminary pharmacokinetic (PK) and safety data from the sentinel participant during the second trimester are expected in the second quarter of 2025. Additional PK and safety data at the time of delivery are anticipated in the third quarter of 2025.
