RLYB212

Fetal and Neonatal Alloimmune Thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare, potentially life-threatening disease that can cause uncontrolled bleeding in fetuses and newborns. There is currently no approved therapy for the prevention of FNAIT.

FNAIT can arise during pregnancy due to incompatibility between a fetus positive for human platelet antigen 1a (HPA-1a) and an HPA-1a negative expectant mother. Estimates suggest that >22,000 pregnancies are at higher risk of FNAIT annually in the EU, North America, and Australia. Rallybio is conducting a multinational FNAIT Natural History Study to better characterize FNAIT risk in broad, diverse populations.

Disease Mechanism

Upon exposure to the fetal HPA-1a antigen, expectant HPA-1a negative mothers can develop antibodies to HPA-1a in a process known as alloimmunization. When alloimmunization occurs, maternal anti-HPA-1a antibodies can cross the placenta and destroy HPA-1a positive platelets in the fetus.

The destruction of fetal platelets can result in severe thrombocytopenia (low platelet counts) in the fetus and potentially lead to intracranial hemorrhage (ICH). ICH can have devastating consequences including miscarriage, stillbirth, or loss of the newborn, or severe lifelong neurological disability in those babies who survive.

RLYB212

RLYB212 is an investigational drug designed to prevent HPA-1a alloimmunization in expectant mothers at higher risk of FNAIT.

RLYB212 is a novel, subcutaneously administered human monoclonal anti-HPA-1a antibody. Administration of RLYB212 is designed to rapidly eliminate HPA-1a positive fetal platelets from an expectant mother’s circulation, thereby preventing maternal HPA-1a alloimmunization. Prevention of maternal alloimmunization eliminates the risk of FNAIT in the fetus.

As part of its RLYB212 program, Rallybio expects to develop a simple diagnostic that can be integrated into current, routine, first trimester screening guidelines and tests in order to identify expectant mothers at higher risk of FNAIT.

RLYB212 Clinical Stage of Development

Phase 1 and proof-of-concept (PoC) Phase 1b studies in healthy volunteers (EU); a non-interventional, multi-center FNAIT Natural History Study, screening expectant mothers (US/EU)

Potential Indication

Prevention of HPA-1a alloimmunization in expectant mothers at higher risk of FNAIT

Disease Mechanism

Platelet antigen mismatch between an expectant mother who is HPA-1a negative and an HPA-1a positive fetus can cause alloimmunization (immune attack) by the mother’s antibodies against fetal platelets.

Disease Impact

Severe thrombocytopenia in the fetus that potentially leads to intracranial hemorrhage (ICH), which can result in miscarriage, stillbirth, or loss of the newborn, or severe, lifelong neurological disability

Therapeutic Modality

Novel monoclonal anti-HPA-1a antibody

Mechanism of Action

RLYB212 is designed to rapidly eliminate HPA-1a positive fetal platelets from an expectant mother’s circulation, thereby preventing HPA-1a alloimmunization and eliminating risk of FNAIT.

Mode of Administration

Subcutaneous injection

Diagnostic

Rallybio also plans to develop a simple diagnostic test to identify expectant mothers at higher risk of FNAIT.

Clinical Program Status

Rallybio announced findings (March 2023) from its Phase 1b (EU) study, demonstrating that a single, subcutaneous dose of RLYB212 rapidly and completely eliminated transfused HPA-1a positive platelets in HPA-1a negative subjects. RLYB212 was associated with a greater than 90% reduction of the mean platelet elimination half-life in both RLYB212 dose groups compared to placebo. The reduction in mean platelet elimination was dose-related, and the broad range of pharmacokinetic and pharmacodynamic data allows substantive modeling to inform dose selection for a future registrational study. Further, RLYB212 has been well-tolerated, and no serious adverse events have been reported to date. These clinical findings and safety profile are consistent with previously reported data.

Rallybio expects to report data from the Phase 1b clinical study of RLYB212 at a scientific conference in 2023.

Rallybio also announced in March 2023 that testing in the multiple dose cohort of its Phase 1 trial in Europe initiated in the first quarter of 2023. This portion of the Phase 1 study will evaluate safety and pharmacokinetics of RLYB212 based on healthy, HPA-1a negative male and female participants receiving up to six doses of RLYB212 over three months. The Company expects results from this cohort of subjects in the fourth quarter of 2023.

Rallybio also has an ongoing prospective, non-interventional, multinational FNAIT Natural History Study to screen expectant mothers for higher FNAIT risk. During the gestation week 10 to 14 prenatal visit, individuals are screened to determine whether they are HPA-1a negative and positive for HLA-DRB3*01:01. The Natural History Study is expected to screen up to 30,000 expectant mothers of different racial and ethnic characteristics in the US and EU and will help further characterize the risk of FNAIT across broad, diverse populations. Data from this study will contribute to a control dataset for a future, single-armed registration trial for RLYB212.