RLYB212 / Rallybio - LARVOL DELTA

Identifying Pregnancies at Higher Risk for HPA-1a Alloimmunization and Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT): An International, Prospective, Natural History Study (ASH 2023) - P | "These data will provide a contemporary control population preceding future single-arm studies of a novel human anti-HPA-1a monoclonal antibody, RLYB212, in prophylaxis of maternal HPA-1a alloimmunization and FNAIT...Inclusion criteria Pregnant women aged ≥18 years Exclusion criteria Prior history of FNAIT or known HPA-1a alloimmunization Statistical methods Demographic, baseline characteristics and discrete variables will be summarized Primary objective To inform frequency of higher FNAIT risk among pregnant women of diverse racial and ethnic characteristics (all comers). (Figure) Secondary objectives Frequency of HPA-1a maternal alloimmunization at Weeks 10–14 postpartum in pregnant women at higher FNAIT risk and outcomes such as: – Spontaneous abortion: non-deliberate fetal death prior to 19 weeks of gestation – Elective abortion: deliberate termination of pregnancy at any time in gestation – Stillbirth: non-deliberate fetal death after 19 weeks of gestation –..."

Clinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Prophylactic Administration of HPA-1a–Specific Antibody RLYB212 Safely Prevents Fetal/Neonatal Alloimmune Thrombocytopenia in Pregnant Mice (ASH 2024) - "Taken together, these data establish that prophylactic administration of the HPA-1a-specific antibody RLYB212 to pregnant mice is both effective and safe in preventing maternal alloimmunization and FNAIT. These preclinical findings further support the potential of RLYB212 as a prophylactic therapy, paving the way for human studies aimed at preventing FNAIT in pregnant women."

Preclinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Mood Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Prophylactic Administration of HPA-1a–Specific Antibody RLYB212 Safely Prevents Fetal/Neonatal Alloimmune Thrombocytopenia in Pregnant Mice (ASH 2024) - "Taken together, these data establish that prophylactic administration of the HPA-1a-specific antibody RLYB212 to pregnant mice is both effective and safe in preventing maternal alloimmunization and FNAIT. These preclinical findings further support the potential of RLYB212 as a prophylactic therapy, paving the way for human studies aimed at preventing FNAIT in pregnant women."

Preclinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Mood Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization (clinicaltrials.gov) - P2 | N=8 | Active, not recruiting | Sponsor: Rallybio | Trial completion date: May 2027 ➔ Jul 2026 | Trial primary completion date: May 2027 ➔ Oct 2025

Trial completion date • Trial primary completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

First Quarter 2025 Financial Results (Businesswire) - "Research & Development (R&D) Expenses: R&D expenses were $5.7 million for the first quarter of 2025, compared to $12.9 million for the same period in 2024. The decrease in R&D expenses was primarily due to a decrease in development costs related to RLYB212, RLYB116, and other program candidates, in addition to a decrease in payroll and personnel-related costs, largely related to the workforce reduction in the first quarter of 2024."

Commercial • Hematological Disorders • Immunology • Thrombocytopenia

Rallybio to Discontinue Development of RLYB212 for Prevention of FNAIT (Rallybio Press Release) - P2 | N=8 | NCT06435845 | Sponsor: Rallybio | "Rallybio...announced the discontinuation of the RLYB212 program for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT). The Company’s decision to discontinue RLYB212 development was based on pharmacokinetic (PK) data from the Phase 2 clinical trial demonstrating the inability of the RLYB212 dose regimen to achieve predicted target concentrations, as well as the minimum target concentration required for efficacy...Second trimester PK results from the sentinel participant demonstrated an inability of RLYB212 to achieve predicted target concentrations of 6 ng/mL to 10 ng/mL, as well as the minimum target concentration required for efficacy of 3 ng/mL, with values near or below the assay’s lower limit of quantitation....No further enrollment in the trial is planned and all screening of participants has been stopped. The Company will continue safety follow-up of the sentinel participant..."

Discontinued • P2 data • Trial termination • Thrombocytopenia

Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization (clinicaltrials.gov) - P2 | N=8 | Active, not recruiting | Sponsor: Rallybio | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Rallybio Announces Initiation of Dosing in RLYB212 Phase 2 Clinical Trial (Businesswire) - "Rallybio Corporation...today announced that the first participant has been dosed in the Phase 2 trial investigating RLYB212 in pregnant women at higher risk for HPA-1a alloimmunization and fetal and neonatal alloimmune thrombocytopenia (FNAIT). Pharmacokinetic (PK) and safety data from the second trimester are expected in the second quarter of 2025, with PK and safety data at the time of delivery expected in the third quarter of 2025....The Phase 2 trial is designed to enroll participants in three stages: first with a sentinel pregnant woman, followed by an initial cohort (Cohort 1) that will include three pregnant women, and then a second cohort (Cohort 2) that will include four pregnant women, for a total target enrollment of eight participants. A data review for participants and infants is planned prior to the initiation of each cohort. The trial will seek to enroll participants at sites in Europe."

P2 data • Trial status • Immunology • Thrombocytopenia

Rallybio Highlights 2024 Accomplishments and Anticipated Milestones for 2025 (Businesswire) - "Rallybio plans to conclude screening in the FNAIT natural history study in the United States and Canada as of January 31, 2025...Anticipated 2025 Key Milestones: RLYB212: i) Initiate dosing of sentinel participant in the Phase 2 trial in the second quarter of 2025; ii) Present interim data from the FNAIT natural history study in mid-2025; iii) Report interim safety and pharmacokinetic (PK) data from the Phase 2 trial sentinel participant in the third quarter of 2025; iv) Completion of pregnancy, with safety and PK data readout, from the Phase 2 trial sentinel participant in the fourth quarter of 2025."

Clinical data • P2 data • Trial status • Hematological Disorders • Thrombocytopenia

Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization (clinicaltrials.gov) - P2 | N=8 | Recruiting | Sponsor: Rallybio IPA, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Informing pregnancy dose via target-mediated drug disposition modeling and simulations for a recombinant human monoclonal antibody. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "A 0.06 mg RLYB212 dose with a loading dose of 0.12 mg was identified as the optimal dosing regimen of RLYB212, which maintained exposures below the target upper boundary of ~10 ng/mL throughout pregnancy. This work presents an application of the TMDD model that advances the quantitative clinical pharmacology toolkit to understand monoclonal antibody PK in pregnancy."

Journal • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

A Phase 1b PK/PD Study to Demonstrate Antigen Elimination With RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention. (PubMed, Thromb Haemost) - "The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies."

Clinical • Journal • P1 data • PK/PD data • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization (clinicaltrials.gov) - P2 | N=8 | Not yet recruiting | Sponsor: Rallybio IPA, LLC

New P2 trial • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura