Rallybio (RLYB) The Citizens JMP Life Sciences Conference 2025 summary

Program updates and strategic focus

• Lead program RLYB212 was discontinued after discovering inability to maintain therapeutic plasma levels in pregnancy, making it unsuitable for preventing FNAIT due to rapid drug clearance at the maternal-fetal interface.

• RLYB116, a Complement Factor 5 inhibitor based on an Affibody platform, is now the lead clinical asset, offering weekly subcutaneous dosing, high stability, and low cost of goods.

• RLYB116 targets indications with unmet needs, notably antiphospholipid syndrome (APS), where current therapies like Warfarin are insufficient for many patients.

• The company is also advancing an ENPP1 inhibitor for hypophosphatasia, with preclinical data expected soon, and maintains a Matriptase 2 antibody program for iron overload syndromes, though progress is limited by capital constraints.

• Partnership with EyePoint is on hold as EyePoint prioritizes its own lead programs.

Clinical development and data plans

• RLYB116 demonstrated rapid, complete, and sustained C5 knockdown in phase I, with improved drug purity addressing prior side effects.

• Upcoming adaptive-design study will start at 150 mg, with flexibility to adjust dose based on emerging data, aiming for optimal efficacy and tolerability.

• Data readouts from the RLYB116 study are planned for Q3 and Q4, with results to be shared cohort by cohort as they become available.

• Safety focus is on tolerability, with previous side effects linked to bacterial contamination now largely resolved.

• For APS, initial studies will use biomarkers in small patient groups before moving to larger outcome-based trials.

Market and scientific outlook

• APS affects 150,000–200,000 in the US, with tens of thousands inadequately managed by current anticoagulants; diagnosis is straightforward via antibody testing.

• Complement Factor 5 remains a validated target with broad clinical success, though other complement pathway inhibitors are also emerging for specific indications.

• Oral complement inhibitors may be less suitable for conditions requiring strict compliance, such as PNH, but could be useful in more indolent diseases.

• There is still significant opportunity for C5 inhibitors in new indications beyond crowded markets like PNH.

• The company’s business model emphasizes acquiring and developing assets with strong scientific rationale for rare diseases.