Rallybio Shifts Focus After Setback in Rare Bleeding Disorder Trial

Rallybio, a Connecticut-based biotech company, has announced a significant pivot in its development strategy following disappointing results from a Phase II trial of its lead molecule, RLYB212. The antibody, designed to treat fetal and neonatal alloimmune thrombocytopenia (FNAIT), failed to reach predicted target concentrations in the dosing trial, prompting the company to discontinue its development.

RLYB212 Trial Results and Discontinuation

The Phase II trial revealed that RLYB212, a human monoclonal antibody, was not achieving the minimum target concentration of 3 ng/mL required for efficacy, let alone the predicted range of 6–10 ng/mL. Stephen Uden, CEO of Rallybio, stated, "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."

This setback represents a significant change in direction for Rallybio, which had positioned RLYB212 as its lead molecule for treating FNAIT, a rare bleeding disorder where a mother's immune system attacks a fetus or newborn's platelets.

Strategic Shift to RLYB116

In light of the RLYB212 discontinuation, Rallybio is redirecting its focus to RLYB116, an antibody fusion protein currently in Phase I trials. This molecule inhibits a protein in the complement pathway, a part of the body's innate immune system. The company is developing RLYB116 for a variety of rare autoimmune disorders, including:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Antiphospholipid syndrome (APS)
• Generalized myasthenia gravis (gMG)

Rallybio's Pipeline and Partnerships

Beyond RLYB116, Rallybio's pipeline remains largely preclinical. The company is developing a small molecule for hypophosphatasia, a rare and inherited metabolic bone disorder, in partnership with Recursion. Additionally, they are working on an antibody for iron overload and anemias.

It's worth noting that RLYB211, another FNAIT-targeting molecule previously highlighted by the company, no longer appears in Rallybio's published pipeline, suggesting a broader reevaluation of their FNAIT program.

Rallybio, which launched in 2018 with nearly $250 million in funding across multiple rounds, continues to focus on developing treatments for rare and ultra-rare conditions. This recent setback and subsequent pivot underscore the challenges and risks inherent in rare disease drug development, as well as the importance of maintaining a diverse pipeline in the biotechnology sector.