Exicure Announces Plans for New Clinical Trial in Acute Myeloid Leukemia (AML)
Exicure, Inc. (Nasdaq: XCUR), a clinical-stage biotechnology company focused on developing innovative therapeutics targeting diseases with high unmet medical needs, announced significant updates today regarding its lead investigational drug candidate, GPC-100 (burixafor). The company is advancing GPC-100 as a promising small molecule inhibitor of CXCR4 and is preparing for a new clinical trial targeting patients with Acute Myeloid Leukemia (AML), a challenging hematologic malignancy.
The clinical development of GPC-100 represents a strategic shift for Exicure as it positions itself to address therapeutic gaps in hematological cancers and transplant-associated therapies. GPC-100 is currently being investigated for its potential to enhance chemotherapy response and improve stem cell mobilization outcomes. With encouraging preclinical and early clinical results, the company is now pursuing broader applications for this asset in oncology and beyond.
Preparing for AML Clinical Trial: A Critical Step Toward Addressing an Aggressive Blood Cancer
Exicure is laying the groundwork for a clinical trial of GPC-100 in Acute Myeloid Leukemia, one of the most aggressive and difficult-to-treat forms of blood cancer. AML arises from the uncontrolled proliferation of abnormal myeloid cells in the bone marrow, leading to impaired hematopoiesis and life-threatening complications. Despite advances in chemotherapy and bone marrow transplantation, survival rates remain dismal—especially for older adults and those with relapsed or refractory disease.
GPC-100 is poised to make an impact by potentially enhancing chemosensitivity in AML patients when used in combination with existing treatment regimens. Exicure aims to build on prior studies conducted by Taigen, the original developer of GPC-100. Taigen previously initiated a Phase 1 clinical study involving 15 patients with relapsed or refractory AML. In that trial, GPC-100 was administered in combination with the standard chemotherapeutic agents fludarabine and cytarabine. The primary objective was to evaluate safety and preliminary efficacy.
While the data from that study were early-stage, the results supported the feasibility of combining GPC-100 with cytotoxic agents. More importantly, they provided a foundation for the development of a new therapeutic strategy centered on modulating the tumor microenvironment and altering leukemic cell migration and survival through CXCR4 inhibition.
Scientific Rationale: Targeting CXCR4 to Enhance Chemotherapy Response
CXCR4, a chemokine receptor expressed on the surface of hematopoietic and leukemic cells, plays a pivotal role in cell trafficking, survival, and drug resistance. Overexpression of CXCR4 has been correlated with poor prognosis in AML and other hematologic malignancies. Inhibition of this receptor can sensitize leukemic cells to chemotherapy, disrupt protective signals from the bone marrow niche, and mobilize cells into peripheral circulation where they become more vulnerable to cytotoxic agents.
The unique mechanism of action of GPC-100, a potent and selective CXCR4 antagonist, opens the door to combination strategies that may amplify therapeutic efficacy in AML. This concept was further validated in recent preclinical research published by Dr. Pam Becker from City of Hope in collaboration with GPCR Therapeutics USA, a wholly owned subsidiary of Exicure.
At the 2024 American Society of Hematology (ASH) Annual Meeting, data presented in Poster #2758 detailed the synergistic effect of dual inhibition of the CXCR4 receptor with GPC-100 and the beta-2 adrenergic receptor pathway blockade. This combination was shown to significantly improve chemotherapy responsiveness in preclinical AML models. The rationale behind this dual-targeting approach lies in disrupting multiple survival pathways simultaneously, thereby reducing the risk of chemoresistance and disease relapse.
This innovative approach is now protected under an expanded patent portfolio, with intellectual property granted in major jurisdictions including the United States, Japan, Australia, and Taiwan. These protections not only secure Exicure’s competitive position but also offer strategic leverage for future partnership and licensing opportunities.
Ongoing Phase 2 Study in Multiple Myeloma: A Key Milestone Ahead
While plans for AML development are progressing, Exicure is also actively advancing GPC-100 in another hematologic indication—multiple myeloma (MM). An ongoing Phase 2 clinical trial is currently evaluating the drug in patients undergoing autologous stem cell transplant (ASCT), a cornerstone treatment modality for eligible MM patients (ClinicalTrials.gov identifier: NCT05561751).
In the context of stem cell transplantation, the ability to mobilize sufficient hematopoietic stem cells from the bone marrow into peripheral blood is crucial for harvesting and reinfusion. GPC-100, due to its CXCR4 antagonism, promotes stem cell mobilization—a mechanism similar to that of the approved agent plerixafor (Mozobil®). However, GPC-100 is orally bioavailable and potentially offers an improved therapeutic window and patient convenience.
The outcome of this trial could serve as a pivotal moment for Exicure. If the data show improved or equivalent stem cell mobilization compared to standard regimens, GPC-100 could become a preferred alternative, particularly in combination with agents like G-CSF or as a standalone mobilizer. The company expects topline data from this study in the fourth quarter of 2025, which could support further clinical advancement or regulatory filings.
Expanding the Horizon: Potential Indications Beyond AML and MM
Exicure is also strategically evaluating additional therapeutic areas where GPC-100’s mechanism could be leveraged. Among these are sickle cell disease, pediatric oncology, and settings involving advanced cell and gene therapies. Each of these areas represents a significant market with considerable clinical challenges—particularly in terms of stem cell mobilization, microenvironmental modulation, and overcoming treatment resistance.
In sickle cell disease, for instance, the mobilization of hematopoietic stem cells is a critical step in the preparation for gene therapy approaches aimed at correcting the defective hemoglobin gene. Agents like GPC-100 could potentially enhance mobilization efficacy and reduce the burden of apheresis procedures.
Similarly, pediatric oncology presents a unique opportunity to tailor CXCR4-targeted therapies to younger patients with chemoresistant or relapsed leukemias. While pediatric trials require careful design and regulatory oversight, the unmet need and opportunity for innovation are significant.
Lastly, the ongoing growth of the cell and gene therapy sector continues to drive demand for reliable and efficient stem cell mobilization platforms. GPC-100 could play a critical role in improving the consistency and effectiveness of stem cell harvests for manufacturing purposes.
Exicure’s current pipeline strategy around GPC-100 highlights the company’s commitment to tackling challenging diseases through mechanism-based innovation. With ongoing trials, a robust patent portfolio, and expanding preclinical data, the company is well-positioned to carve out a leadership role in the CXCR4-targeted therapy space.
In parallel with its clinical execution, Exicure is expected to explore strategic collaborations and licensing opportunities to accelerate development and broaden global access to GPC-100. Whether through partnerships with academic centers, co-development agreements with larger pharmaceutical firms, or expansion into ex-U.S. markets, the momentum around GPC-100 appears to be building.
As the biotech industry increasingly looks to targeted agents that improve upon existing standards of care, Exicure’s progress with GPC-100 will be closely watched—particularly with the anticipated readout from its multiple myeloma trial and the initiation of its AML program.
In a landscape marked by both high risk and high reward, Exicure’s science-driven approach and therapeutic ambition could very well pay off—not only for the company but also for the patients desperately in need of more effective and better-tolerated treatment options.
