Rallybio Announces Proof-of-Concept Results and Development Updates for RLYB212, a Novel Monoclonal anti-HPA-1a Antibody to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia
-- RLYB212 Demonstrated Dose-Dependent, Rapid and Complete Elimination of Transfused HPA-1a Positive Platelets in HPA-1a Negative Subjects --
-- Mean Reduction in
-- Phase 2 Study in Pregnant Women at Higher Risk of HPA-1a Alloimmunization to be Initiated in 2H 2024 --
-- Phase 1 Multiple Dose Data and Maternal-Fetal Toxicology Data On-track for 4Q 2023 --
-- Company to Host Investor and Analyst Meeting Webcast with Corresponding Slides at
Phase 1b Proof-of-Concept (POC) Study of RLYB212 in FNAIT
The Phase 1b single-blind, placebo-controlled proof-of-concept study was designed to establish the ability of SC RLYB212 to rapidly eliminate HPA-1a positive platelets transfused to HPA-1a negative healthy subjects. The study included 11 males aged 18 to 65 years, randomized to RLYB212 0.09mg (n=4), RLYB212 0.29mg (n=5), or placebo (n=2).
Summary of Proof-of-Concept Results
- RLYB212 demonstrated a dose-dependent, rapid and complete elimination of transfused HPA-1a positive platelets in HPA-1a negative subjects.
- Mean platelet elimination half-life was 5.8 hours (0.09mg) and 1.5 hours (0.29mg) for RLYB212 compared to 71.7 hours for placebo, meeting the study’s prespecified criteria for proof-of-concept in both dose groups (≥ 90% reduction in mean platelet elimination half-life).
- The study’s broad range of pharmacodynamic and pharmacokinetic (PK) data will allow substantive modeling of the RLYB212 concentration-effect relationship and inform the target dose regimen for the planned future studies.
- Platelet elimination profiles after SC administration of RLYB212 were consistent with those of Rhesus factor D (RhD)-positive erythrocytes after intramuscular administration of anti-RhD agents, which are well-established to safely and effectively prevent RhD alloimmunization during pregnancy.
- Consistent with previously reported data, RLYB212 was observed to be well-tolerated with no reports of serious or severe adverse events.
“The data reported today at ISTH continue to support our belief in the potential use of subcutaneous RLYB212 as a prophylactic therapeutic for the prevention of HPA-1a alloimmunization and FNAIT. We are pleased to see rapid and complete platelet elimination in our target concentration range, with both dose groups meeting the proof-of-concept criteria of at least 90% reduction in mean platelet elimination half-life,” commented Róisín Armstrong, Ph.D., Rallybio’s RLYB212 Program Lead. “With no currently approved therapies for the prevention of FNAIT, there remains a substantial unmet need for a treatment that can effectively eliminate fetal platelet antigen and, as a result, significantly decrease the risk of severe bleeding in the fetus and neonate, including intracranial hemorrhage and its devastating consequences.”
Clinical Development Update for RLYB212
RLYB212 Catalysts for 2023
Rallybioremains on track to complete the following RLYB212 milestones in the fourth quarter of 2023:
- Comprehensive toxicology program, including maternal-fetal toxicology
- Multiple dose cohort of Phase 1 safety and PK study
Phase 2 Dose Confirmation Study
- The Company plans to initiate a Phase 2 dose confirmation study in the second half of 2024, designed to confirm the RLYB212 dose regimen in pregnant women at higher risk of FNAIT prior to initiation of a larger Phase 3 registrational study.
- This study will employ a sentinel, sequenced cohort design to allow for any required adjustments to the dose regimen, prior to advancing the confirmed dose regimen into the registrational study.
Natural History Study
- The Natural History Study is designed to provide a contemporary dataset for HPA-1a alloimmunization frequency in a racially and ethnically diverse population that can serve as a control for the planned single-arm registrational study, along with establishing the operational framework for seamless initiation of the Phase 2 study and future Phase 3 registrational study.
- The Natural History Study has screened approximately 4,500 women to date and an estimated 7,600 women are planned to be screened by end of 2023.
Screening for the Natural History Study is expected to continue simultaneously with execution of the Phase 2 study; data from both studies will be used for end of Phase 2 regulatory discussions with the
U.S. Food and Drug Administrationand the European Medicines Agencyto support design and initiation of the Phase 3 registrational study.
Phase 3 Registrational Study
Following completion of the Phase 2 dose confirmation study,
Rallybioexpects to commence a Phase 3 registrational study, after consultation with regulatory authorities.
Investor and Analyst Meeting Webcast
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.
This press release contains forward-looking statements that are based on our management’s beliefs and assumptions and on currently available information. All statements, other than statements of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements concerning results from the RLYB212 Phase 1b proof-of-concept study, statements concerning the substance, design and timing of our planned or ongoing studies for RLYB212, including the planned Phase 2 study and Phase 3 registrational study, the timing of the availability of data from such studies, our expectations regarding reporting of data from such studies, our expectations regarding the usefulness of such data, the success of modeling to inform dosing for a future registrational study, our ability to advance RLYB212 into future clinical studies, the outcomes of discussions with healthcare authorities, including the FDA, and the likelihood that
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