Hypophosphatasia

– RLYB212 Phase 2 PK Results Did Not Achieve Target Concentrations, Including Minimum Target Concentration Required for Efficacy – – RLYB116 Confirmatory PK/PD Study to Initiate in 2Q 2025, with Data in 2H 2025 – NEW HAVEN, CT, USA I April 08, 2025 I Rallybio Corporation (Nasdaq: RLYB), a clinical-stage biotechnology company translating scientific advances into transformative therapies for patients with devastating rare diseases, today 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. Rallybio remains focused on advancing RLYB116, a once-weekly low volume C5 inhibitor for the treatment of complement-driven diseases, as well as its emerging preclinical programs. “We are disappointed by the PK results of the RLYB212 Phase 2 trial,” said Stephen Uden, M.D., Chief Executive Officer of Rallybio. “Given that the results significantly deviated from the predicted range and the absence of empiric data to further inform dose adjustment, the risk/benefit no longer supports continued dosing, and we will discontinue RLYB212 development. We are grateful to the participants, investigators, and study staff for their partnership and dedication to this program.” Dr. Uden continued, “Rallybio remains steadfast in our mission to develop transformative therapies. We are focused on creating shareholder value by advancing our portfolio of potentially best-in-class assets for patients with rare diseases, which includes RLYB116 and REV102, an ENPP1 inhibitor for patients with hypophosphatasia, as well as RLYB332, a long-acting matriptase-2 antibody for diseases of iron overload.” RLYB212 Phase 2 Trial The single-arm Phase 2 dose confirmation trial was designed to assess the PK and safety of RLYB212 in pregnant women at higher risk for HPA-1a alloimmunization and FNAIT. Secondary objectives included the assessment of pregnancy and neonatal/infant outcomes, and the occurrence of emergent HPA-1a alloimmunization. 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. Dose adjustment is not deemed feasible given that PK levels are meaningfully outside the predicted range and the absence of empiric data to inform an adjustment. It is hypothesized that HPA-1a antigen expression on the placenta may be impacting plasma concentrations of RLYB212. 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 as specified in the clinical trial protocol. Promising Rare Disease Pipeline to Deliver Data in 2H 2025 RLYB116 Program Rallybio remains on track to initiate dosing in the RLYB116 confirmatory clinical pharmacokinetic/ pharmacodynamic (PK/PD) study in the second quarter of 2025, with data readouts from Cohorts 1 and 2 expected in the third and fourth quarter of 2025, respectively. The study is expected to demonstrate complete and sustained complement inhibition with improved tolerability of RLYB116. RLYB116 is a novel antibody mimetic fusion protein designed to inhibit C5 and to provide a once-weekly, small volume, subcutaneously injected therapy to meet patient demand for a convenient, self-administered at-home solution. RLYB116 has the potential to address significant unmet need for patients across a number of complement mediated diseases, including paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome (APS), and generalized myasthenia gravis (gMG), which together represent a commercial opportunity of more than $6 billion. Importantly, this strategic focus on complement-mediated diseases presents a unique opportunity for Rallybio to utilize its team’s deep domain experience in successfully designing, developing, and delivering complement inhibitors for patients with rare diseases. Preclinical Programs REV102, an ENPP1 inhibitor for the treatment of patients with HPP under development through a joint venture with Recursion Pharmaceuticals, entered investigational new drug application (IND)-enabling studies in the first quarter of 2025 to support the initiation of a Phase 1 study in 2026. Data evaluating REV102 in a preclinical model of later-onset HPP is expected in the second half of 2025. Rallybio’s portfolio also includes RLYB332, a long-acting, monoclonal anti-matriptase-2 antibody that has the potential to be a best-in-class treatment for diseases of iron overload. Preclinical data has demonstrated superior impact on PD parameters relative to comparator molecules, including on serum iron, unsaturated iron binding capacity (UIBC), and transferrin saturation (TSAT). The Company is preparing plans for future development of RLYB332. 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 pipeline of promising product candidates aimed at addressing diseases with unmet medical need in areas of complement dysregulation, hematology, and metabolic disorders. The Company’s lead program, RLYB116, is a differentiated C5 inhibitor with the potential to treat diseases of complement dysregulation. Rallybio also has two programs in preclinical development, including REV102, an ENPP1 inhibitor for the treatment of patients with hypophosphatasia (HPP), and RLYB332, a long-acting matriptase-2 antibody for the treatment of diseases of iron overload. Rallybio is headquartered in New Haven, Connecticut. For more information, please visit www.rallybio.com and follow us on LinkedIn and Twitter . SOURCE: Rallybio

iStock, Andrii Yalanskyi The company is dropping its former lead molecule in favor of another antibody, RLYB116, which is being developed for a variety of rare autoimmune disorders. Rallybio is discontinuing the development of its former lead molecule in a rare autoimmune bleeding disorder. The biotech’s decision, announced Tuesday, comes after a disappointing pharmacokinetic readout from a Phase II trial. RLYB212 is a human monoclonal antibody the company was developing to treat fetal and neonatal alloimmune thrombocytopenia (FNAIT), a rare bleeding disorder in which a mother’s immune system attacks a fetus or newborn’s platelets. Rallybio’s data showed that the antibody was not reaching predicted target concentrations (6–10 ng/mL) or the minimum target concentration required for efficacy (3 ng/mL). “Given that the results significantly deviated from the predicted range and the absence of empiric data to further inform dose adjustment, the risk/benefit no longer supports continued dosing, and we will discontinue RLYB212 development,” CEO Stephen Uden said in the statement. The Connecticut-based company will continue development on another molecule, RLYB116, an antibody fusion protein that inhibits a protein in the complement pathway, a part of the body’s innate immune system. Rallybio is pushing RLYB116, currently in Phase I trials , for diseases resulting in rare disorders of the complement pathway, including paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome (APS) and generalized myasthenia gravis (gMG). The discontinuation is a fork in the road for Rallybio. The company launched in 2018, backed by multiple funding rounds totaling nearly $250 million, to investigate new treatments for rare and ultrarare conditions. In addition to RLYB212’s discontinuation, molecules like RLYB211, another FNAIT-targeting molecule it had previously touted , no longer appears in the company’s published pipeline . Other than RLYB116, the company’s pipeline is preclinical and includes a small molecule for hypophosphatasia, a rare and inherited metabolic bone disorder, discovered in a research partnership with Recursion, and an antibody for iron overload and anemias.

The funds raised will be directed towards generating clinical proof-of-concept for BE-101 in the ongoing BeCoMe-9 Phase I/II trial. Credit: skipper_sr/Shutterstock. Be Biopharma has secured $92m in a Series C financing round to advance its clinical programmes for haemophilia B and hypophosphatasia. New investor Nextech participated in the round, which also received contributions from current investors such as Bristol Myers Squibb, ARCH Venture Partners, RA Capital Management, Atlas Ventures and Alta Partners. The funds will be directed towards generating clinical proof-of-concept for the company’s B cell medicine (BCM), BE-101, in the BeCoMe-9 Phase I/II trial underway for individuals with haemophilia B. The proceeds will support the advancement of BE-102, a treatment for hypophosphatasia, into clinical testing. Both programmes are underpinned by the company’s BCM product platform. The company has also announced that Melissa McCracken from Nextech, a Switzerland-based venture capital firm, will join the board of directors of Be Bio. Be Bio CEO Joanne Smith-Farrell stated: “With this funding in hand, we are well-equipped to advance our two lead programmes and solidify our position as a multi-programme, clinical-stage company. “We are on track to demonstrate clinical proof-of-concept for BE-101 in haemophilia B this year.  Additionally, BE-102 is poised to enter the clinic next year, potentially demonstrating BCMs’ potential to become a new gold standard in enzyme replacement by providing hypophosphatasia patients with a transformative new option.” BE-101 is designed to continuously express active Factor IX (FIX) following a single infusion. The US Food and Drug Administration granted investigational new drug clearance in May 2024 followed by fast track status in September. Another BCM targeting hypophosphatasia (HPP), BE-102 leverages artificial intelligence-guided protein design for modifying primary human B cells to produce the alkaline phosphatase enzyme, which is deficient in individuals with HPP.