9 March 2023 - - Clinical proof-of-concept has been achieved in a Phase 1b study for RLYB212, an anti-HPA-1a monoclonal antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT), US-based Rallybio Corp. (NASDAQ: RLYB) said.

Results show that one week after a single subcutaneous dose, RLYB212 was able to rapidly and completely eliminate transfused, HPA-1a positive platelets in HPA-1a negative subjects.

Additional findings from the study show:

The reduction in mean platelet elimination half-life was greater than 90% in both RLYB212 dose groups compared to placebo and was dose related.

The broad range of pharmacokinetic and pharmacodynamic data allows substantive modeling to inform dose selection for a future registrational study.

RLYB212 was observed to be well-tolerated with no serious adverse events reported.
The company expects to report data from the Phase 1b clinical study of RLYB212 at a scientific conference in 2023.

Rallybio also announced today that testing in the multi-dose cohort of its single-center Phase 1 trial in Europe began in the first quarter of 2023.

This portion of the Phase 1 study will evaluate safety and pharmacokinetics of RLYB212 based on repeat dosing over 12 weeks in healthy male and female participants. The company expects results from this cohort of subjects in the fourth quarter of 2023.

Given the favorable development profile of RLYB212 to date, the data generated to date for RLYB212, and the expected manufacturing and supply efficiencies for RLYB212, the company also announced today that RLYB211, a plasma-derived polyclonal anti-HPA-1a antibody, will not be advanced further in clinical development.

Rallybio's Phase 1b study is a single-blind, placebo-controlled proof-of-concept study designed to establish the ability of subcutaneous RLYB212 to rapidly accelerate the elimination of HPA-1a positive platelets transfused to HPA-1a negative healthy male participants.

In this single-center, EU-based study, the elimination of transfused platelets serves as a surrogate for assessing the ability of an anti-HPA-1a antibody to drive rapid elimination of HPA-1a positive fetal platelets from an expectant mother's circulation, thereby potentially preventing HPA-1a maternal alloimmunization and the occurrence of FNAIT in fetuses and newborns.

The platelet challenge in this model represents an equivalent fetal maternal hemorrhage of 30 mL, a rare and catastrophic scenario during pregnancy.

In August 2022, the company amended the Phase 1b protocol to include a higher dose of RLYB212 and further broaden the range of pharmacokinetic and pharmacodynamic data for RLYB212, enabling substantive modeling of the concentration-effect relationship that can inform dosing for a future registrational study.

The Phase 1b study has been conducted at the Clinical Research department of the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, in Frankfurt/Main, Germany, in collaboration with the Institute of Transfusion Medicine and Immunohaematology, German Red Cross (Deutsches Rotes Kreuz) Blood Transfusion Service Baden-Württemberg-Hessen gGmbH in Frankfurt/Main, Germany.

Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is a potentially life-threatening rare disease that can cause uncontrolled bleeding in fetuses and newborns.

FNAIT can arise during pregnancy due to an immune incompatibility between an expectant mother and her fetus in a specific platelet antigen called human platelet antigen 1, or HPA-1.

There are two predominant forms of HPA-1, known as HPA-1a and HPA-1b, which are expressed on the surface of platelets.

Individuals who are homozygous for HPA-1b, meaning that they have two copies of the HPA-1b allele and no copies of the HPA-1a allele, are also known as HPA-1a negative.

Upon exposure to the HPA-1a antigen, these individuals can develop antibodies to that antigen in a process known as alloimmunization.

In expectant mothers, alloimmunization can occur upon mixing of fetal blood with maternal blood.

When alloimmunization occurs in an expectant mother, the anti-HPA-1a antibodies that develop in the mother can cross the placenta and destroy platelets in the fetus.

The destruction of platelets in the fetus can result in severely low platelet counts, or thrombocytopenia, and potentially lead to devastating consequences including miscarriage, stillbirth, death of the newborn, or severe lifelong neurological disability in those babies who survive.

There is currently no approved therapy for the prevention or prenatal treatment of FNAIT.

Rallybio is a clinical-stage biotechnology company committed to identifying and accelerating the development of life-transforming therapies for patients with severe and rare diseases.

Since its launch in January 2018, Rallybio has built a portfolio of promising product candidates, which are now in development to address rare diseases in the areas of hematology, immuno-inflammation, maternal fetal health, and metabolic disorders.

The company's mission is being advanced by a team of highly experienced biopharma industry leaders with extensive research, development, and rare disease expertise.

Rallybio is headquartered in New Haven, Connecticut, with an additional facility at the University of Connecticut's Technology Incubation Program in Farmington, Connecticut.