New composition for improvement of bone marrow reconstitution and peripheral recovery of neutrophil and platelet counts

The sequential treatment of HSPCs with a prostacyclin analogue, adenylate cyclase sensitizer, and calcimimetic enhances engraftment and lineage reconstitution, addressing the inefficiencies in current transplantation methods by promoting rapid recovery and reducing transplant failure risks.

WO2025172541A1 Publication Date: 2025-08-21AOP ORPHAN PHARMA AG
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Patent Information

Application Number
PCT/EP2025/054046
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-11-06
Filing Date
2025-02-14
Publication Date
2025-08-21

AI Technical Summary

Technical Problem

Current methods for hematopoietic stem and progenitor cell (HSPC) transplantation face challenges in achieving rapid and efficient engraftment and lineage reconstitution, particularly in cases of limited cell numbers, leading to prolonged aplastic phases and increased risk of transplant failure.

Method used

A sequential regimen involving ex vivo priming of HSPCs with a prostacyclin analogue and an adenylate cyclase sensitizer, followed by administration of a calcimimetic to the recipient, enhances engraftment and lineage reconstitution by stimulating migration, adhesion, and differentiation of HSPCs.

Benefits of technology

This approach significantly reduces the time to engraftment, decreases hospitalization days, and lowers healthcare resource utilization by increasing the potency and efficacy of HSPCs, even with low cell doses, thereby reducing the risk of transplant failure and accelerating peripheral blood recovery.

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Abstract

The present invention refers to a new use of a composition comprising a calcimimetic for enhancing engraftment and lineage reconstitution of hematopoietic stem and progenitor cells (HSPCs) in hematopoietic cell transplantation (HCT) recipients, wherein before transplantation, said HSPCs are pre-treated in vitro ("primed") with a prostacyclin analogue and an adenylate cyclase sensitizer, and the composition is administered shortly before, or at the time of transplantation of said HSPCs, and after transplantation of said HSPCs. The invention further refers to a therapeutic combination comprising HSPCs and a calcimimetic and a method for enhancing engraftment capabilities of HSPCs.
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