A clinical-stage biotechnology company committed to identifying and accelerating the development of life-transforming therapies for patients with severe and rare diseases, today reported data from the Phase 1b proof-of-concept study of RLYB212, a novel monoclonal anti-HPA-1a antibody in development for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT). The data, delivered in an oral presentation by Christof Geisen, M.D., at the 31st Congress of the International Society on Thrombosis and Haemostasis (ISTH), showed that subcutaneous (SC) RLYB212 administration produced a dose-dependent, rapid and complete elimination of transfused HPA-1a positive platelets in HPA-1a negative subjects, with both doses meeting the prespecified proof-of-concept criteria of ≥90% reduction in mean platelet elimination half-life. 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.
Christof Geisen, M.D., Institute of Transfusion Medicine and Immunohaematology, German Red Cross Blood Transfusion Service, and the lead author for the RLYB212 abstract stated, “These proof-of-concept results provide further understanding as to how FNAIT may have the potential to be prevented through the rapid and complete elimination of fetal platelet antigens prior to maternal alloimmunization. These data are a critical step forward to address a significant unmet need with no currently approved treatments or therapies to prevent maternal alloimmunization as well as the occurrence of FNAIT in babies.”
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.”
Dr. Armstrong continued, “We continue to focus our efforts on completing 12-week repeat dosing in the Phase 1 safety and PK study of RLYB212, along with the ongoing toxicology program, both of which are on track for the fourth quarter of 2023. In the second half of 2024 we plan to commence a Phase 2 study in pregnant women at higher risk of HPA-1a alloimmunization, designed to confirm the RLYB212 dose regimen for our Phase 3 registrational study. We are also planning for discussions with regulators later in 2023 or in the first half of 2024 in advance of the Phase 2 study.”
Clinical Development Update for RLYB212
Rallybio will host an investor and analyst meeting beginning at 4:00 p.m. ET to discuss clinical development plans for RLYB212.
RLYB212 Catalysts for 2023
- Rallybio remains 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 Administration and the European Medicines Agency to support design and initiation of the Phase 3 registrational study.
Phase 3 Registrational Study
- Following completion of the Phase 2 dose confirmation study, Rallybio expects to commence a Phase 3 registrational study, after consultation with regulatory authorities.
Investor and Analyst Meeting Webcast
Rallybio will host an investor and analyst meeting on Saturday, June 24, 2023 from 4:00 to 6:00 p.m. Eastern Time. The webcast and corresponding slides can be accessed through the Events and Presentations section of Rallybio’s website at http://www.rallybio.com.
About FNAIT
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.
About Rallybio
Rallybio (NASDAQ: RLYB) is a clinical-stage biotechnology company with a mission to develop and commercialize life-transforming therapies for patients with severe and rare diseases. Rallybio has built a broad pipeline of promising product candidates aimed at addressing diseases with unmet medical need in areas of maternal fetal health, complement dysregulation, hematology, and metabolic disorders. The Company has two clinical stage programs: RLYB212, an anti-HPA-1a antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) and RLYB116, a C5 complement inhibitor with the potential to treat several diseases of complement dysregulation, as well as additional programs in preclinical development.
Rallybio is headquartered in New Haven, Connecticut with an additional facility at the University of Connecticut’s Technology Incubation Program in Farmington, Connecticut.
Source: https://www.businesswire.com/
