burixafor (GPC-100) / TaiGen, GPCR Therap, Exicure - LARVOL DELTA

Exicure Completes Patient Enrollment in Phase 2 Study of GPC-100 for Stem Cell Mobilization in Multiple Myeloma Patients Undergoing Autologous Transplant (Businesswire) - "Exicure...announced it has completed patient enrollment in its ongoing Phase 2 clinical trial (NCT05561751) evaluating the safety and efficacy of GPC-100 (burixafor) in combination with propranolol and G-CSF in multiple myeloma patients undergoing autologous stem cell transplant (ASCT). The randomized, open-label, multicenter study is designed to assess whether GPC-100, a small molecule CXCR4 antagonist, can improve CD34+ hematopoietic stem cell mobilization from the bone marrow into the peripheral blood, where they can be collected via leukapheresis for use in ASCT. Topline results from the study are expected in Fall 2025."

Enrollment closed • P2 data • Multiple Myeloma

Exicure, Inc. (Nasdaq: XCUR) Nears Completion of Phase 2 Study of GPC-100 in Multiple Myeloma (Businesswire) - "Exicure...announced that GPCR Therapeutics USA, a subsidiary of Exicure Inc., has dosed the 19th patient in its ongoing Phase 2 clinical trial evaluating GPC-100 (burixafor), a small molecule CXCR4 inhibitor, for the mobilization of stem cells in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) (NCT05561751). The study is an open-label, multi-center trial evaluating the safety and efficacy of GPC-100 and propranolol in combination with G-CSF....This trial is expected to finish patient recruitment at the end of April."

Trial status • Multiple Myeloma

Exicure, Inc. (Nasdaq: XCUR) Announces Their Next Step in Planning for a New Clinical Trial in Acute Myeloid Leukemia (AML) (Businesswire) - "Exicure...shared updates on its lead asset, GPC-100 (burixafor), a small molecule CXCR4 inhibitor. Exicure...is planning for a clinical trial in Acute Myeloid Leukemia (AML) with GPC-100. The company believes that GPC-100, when paired with modern AML treatment regimens, can further improve outcomes in this high unmet need clinical indication....In addition to AML, GPC-100 is currently being evaluated in an ongoing Phase 2 trial in patients with multiple myeloma (MM) undergoing autologous stem cell transplant (ASCT; NCT05561751). Clinical trial results for this study are expected in Q4 2025."

New trial • P2 data • Acute Myelogenous Leukemia • Multiple Myeloma

Pharmacological characterization of a clinical candidate, TG-0054, a small molecule inverse agonist targeting CXCR4. (PubMed, Mol Pharmacol) - "Compared with the clinically used antagonist AMD3100 and the prototypical inverse agonist Isothiourea-1t (IT1t), TG-0054 displayed a unique pharmacological profile. SIGNIFICANCE STATEMENT: CXCR4-targeted therapeutics hold important potential for the treatment of blood cancers. TG-0054 has inverse agonistic properties and is a non-CXCR4-monomerizing small molecule antagonist, unlike other well studied CXCR4 small molecule antagonists."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Multiple Myeloma • Oncology • Transplantation • ARRB1 • CXCL12 • CXCR4

Exicure, Inc. (Nasdaq: XCUR) Announces Issuance of New Patent in Australia (Businesswire) - "Exicure...announced that the Australian Patent Office has issued Patent No. 2018388302, titled 'GPCR Heteromer Inhibitors and Uses Thereof.' This patent covers the company’s innovative combination approach to cancer treatment, specifically targeting CXCR4 and GPCRx. The newly granted patent supports Exicure’s ongoing Phase 2 clinical trial (NCT05561751), which evaluates the combination of GPC-100 and propranolol in multiple myeloma patients. This method aims to improve hematopoietic stem cell mobilization by co-targeting CXCR4 and ADRB2, thereby enhancing the efficacy of CXCR4 inhibitors like GPC-100....This patent family has already been granted in the United States, Japan, and Taiwan, with applications pending in other key jurisdictions."

Patent • Multiple Myeloma

Pina Cardarelli, CEO of GPC USA: “Phase 2 clinical trial in the US is progressing smoothly, aiming for announcement in September” [Google translation] (Money Today) - "'Two more patients will receive 'GPC-100' this month. We aim to complete administering the drug to 20 patients by April and announce the clinical trial results in September...'"

P2 data • Trial status • Multiple Myeloma

An Open-Label, Multi-Center Phase 2 Study to Assess the Safety and Efficacy of Burixafor (GPC-100) and Propranolol with G-CSF for the Mobilization of Stem Cells in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant (ASH 2024) - P2 | "Newer therapies, such as daratumumab, may also have a negative impact on mobilization, supporting a need for an alternative mobilization regimen. Notably, burixafor allowed for same day administration of both mobilizing agent and leukapheresis. This quick kinetics of mobilization is differentiated from the FDA approved plerixafor or motixafortide, which require overnight pre-treatment prior to leukapheresis."

Clinical • P2 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Transplantation • CD34 • CXCR4

Exicure, Inc. Partners with GPCR Therapeutics to Fuel New Growth in Biotech (Businesswire) - "Exicure...has announced the signing of a Memorandum of Understanding (MOU) with GPCR Therapeutics...on December 24, 2024, aimed at the acquisition of GPCR USA, a subsidiary of GPCR Therapeutics, and the technology transfer and collaborative research on GPCR Therapeutics’ ongoing drug development pipelines. Through this acquisition, Exicure plans to secure key technical personnel by purchasing all shares of GPCR USA held by GPCR Therapeutics. Following this, Exicure intends to receive technology transfer for GPCR Therapeutics’ CXCR4 inhibitor, which is currently in Phase 2 clinical trials with the FDA, along with its related patents and intellectual property (IP)....GPCR Therapeutics plans to successfully finalize ongoing clinical trials involving stem cell mobilizers (SCM) targeting multiple myeloma patients and prepare for clinical studies related to acute myeloid leukemia (AML)."

M&A • Acute Myelogenous Leukemia • Multiple Myeloma

Dual Inhibition of CXCR4 and Claudin-18 Isoform X1 in Gastric Adenocarcinoma: An in Silico Study (IGICC 2024) - "This study represents a comprehensive in silico investigation into the simultaneous targeting of CXCR4 and Claudin-18 isoform X1. The data obtained underscore the potential of multimodal targeting strategies in the treatment of gastric adenocarcinoma and demonstrate the efficacy of in silico methods in rational drug design processes. The identification of Burixafor and Mavorixafor as dual-targeted agents establishes a robust molecular foundation for preclinical and clinical studies."

Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • CXCR4

Combined CXCR-4 Inhibition with Novel Agent GPC-100 (burixafor) and Beta 2 Adrenergic Receptor Blockade Enhances Cytarabine Response for Acute Myeloid Leukemia Blasts on Stroma (ASH 2024) - P1 | "The CXCR4 inhibitor plerixafor improves yields of mobilized normal hematopoietic stem cells (HSCs) in combination with filgrastim (G-CSF). Clinical trials of CXCR4 inhibitors have been conducted to mobilize AML out of the protected BM niche, including plerixafor with 7+3 or MEC, BL-8040 with cytarabine (araC), LY2510924 with idarubicin/araC, and ulocuplumab (human IgG4 antibody) with MEC...In addition, high throughput drug screening of AML on stroma, but not in suspension or on CXCL12 coated plates, revealed that combination of the CXCR4 inhibitor GPC-100 and beta blocker propranolol, with araC, increased drug sensitivity (reduced IC50 by ≥4 to >10 fold) as compared to araC alone for AML cells on HS-5 human stromal cell line or autologous patient mesenchymal stromal cells...Conclusions : These studies support further investigation of whether simultaneous blockade of CXCR4 and ADRB2 may potentiate chemotherapy response in AML, perhaps by disrupting..."

Stroma • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ADRB2 • CD58 • CXCL12 • CXCR4 • FLT3 • NPM1 • TP53

GPC Approved for Orphan Drug Designation in the U.S. [Google translation] (HIT News) - "GPCR...a company specializing in new drug development, announced on the 29th that it has received orphan drug designation (ODD) from the US Food and Drug Administration (FDA) for its hematopoietic stem cell activator, which is currently undergoing phase 2 clinical trials in the United States...The clinical trial of hematopoietic stem cell activator, which is being conducted by GPC at 10 hospitals in the United States...The results will be presented at the American Society of Hematology (ASH) meeting in December."

Orphan drug • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Strategy to Improve Functional T-Cell Yield in Peripheral Blood By Co-Inhibition of Beta-2 Adrenergic and CXCR4 Signaling Pathways (ASH 2024) - P2 | "A significant increase in PB lymphocyte count was only observed when propranolol was combined with GPC-100, but not with AMD3100 or BL8040...Treatment of stimulated PBMC with epinephrine inhibited IFNy release, which was fully reversed when propranolol and GPC-100 were added...Therefore, we propose that propranolol can be safely combined with GPC-100 for improving CAR-T efficiency. Comprehensive analysis of immune cell subsets mobilized by propranolol and GPC-100 in our clinical study (NCT05561751) is also ongoing to evaluate this treatment for improving current approaches to cell and gene therapy."

Gene Therapies • Hematological Malignancies • Multiple Myeloma • Oncology • CD4 • CD8 • CXCR4 • GZMB • IFNG

Combined CXCR-4 Inhibition with Novel Agent GPC-100 (burixafor) and Beta 2 Adrenergic Receptor Blockade Enhances Cytarabine Response for Acute Myeloid Leukemia Blasts on Stroma [Google translation] (BioTimes) - "GPCRL...announced on the 21st that it will present a poster on a strategy to effectively treat acute myeloid leukemia (AML) at the American Society of Hematology Annual Meeting (ASH 2024), to be held in San Diego, USA from the 7th to the 10th of next month (local time)....The results of the analysis confirmed that when CXCR4 and ADRB2 are co-inhibited through combination therapy with the company's core pipeline GPC-100 and propranolol in AML patient-derived cells, the anticancer efficacy of cytarabine (AraC), an AML chemotherapy drug, increases by more than 10-fold."

Preclinical • Acute Myelogenous Leukemia

Ph2, Study to Assess the Safety and Efficacy of GPC 100 and Propranolol With and Without G-CSF for the Mobilization of Stem Cells in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: GPCR Therapeutics, Inc. | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Toward optimizing CXCR4 inhibition with beta adrenergic blockade to enhance chemotherapy response in acute myeloid leukemia (AACR 2024) - "The CXCR4 inhibitor plerixafor is used to increase mobilization of peripheral blood stem cells in combination with filgrastim...These have included use of plerixafor with 7+3 or MEC, BL-8040 with cytarabine, and ulocuplumab with MEC...The objective of this preclinical study is to identify the AML patient population most likely to respond to CXCR4 inhibition, and the role of combined beta-adrenergic blockade, as the latter has been shown pre-clinically to augment mobilization of HSCs when combined with a CXCR4 inhibitor, GPC-100 (Sukhtankar et al... These studies support further investigation of whether simultaneous blockade of CXCR4 and ADBR2 may potentiate chemotherapy response in AML by limiting microenvironment mediated chemotherapy protection and reveal that patients with new diagnosis may be more susceptible to this approach."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ADRB2 • CD123 • CD34 • CXCL12 • CXCR4 • FLT3 • IL3RA • NPM1 • PTPRC

Combination of Propranolol and a Novel CXCR4 Antagonist Burixafor (GPC-100) for Enhanced Hematopoietic Cell Mobilization (ASH 2023) - P2 | "In cell-based assays, co-activation of both receptors with their respective ligands, CXCL12 and epinephrine, leads to a synergistic increase in calcium flux (Figure 1) as well as ß-arrestin recruitment, indicating functional consequences of the heteromerization...For comparison, plerixafor increased CD8+ T cell mobilization by only 2-fold...We anticipate that our clinical studies can fill the gap in the current standard of care without adding a significant financial burden or co-morbidities. Furthermore, enhanced mobilization of CD8+ T cells can provide extended opportunities for improved adoptive cell therapies."

Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Multiple Myeloma • Oncology • Sickle Cell Disease • Transplantation • CD8 • CXCL12

Trial in Progress: An Open-Label, Multi-Center Phase 2 Study to Assess the Safety and Efficacy of Burixafor (GPC-100) and Propranolol with and without G-CSF for the Mobilization of Stem Cells in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant (ASH 2023) - P2 | "Key secondary objectives include: assessment of safety and tolerability of GPC-100 and propranolol with and without G-CSF, evaluation of the pharmacodynamics by determining levels of circulating CD34 + cell counts and levels of the chemokine CXCL12 in peripheral blood, and assessment of mean time to ANC and platelet count recovery after ASCT. Exploratory objectives are also included to discover key biomarkers for patient selection, to evaluate cancer/stem/immune cell profiles, and to evaluate treatment impact on patient quality of life."

Clinical • P2 data • Bone Marrow Transplantation • Cardiovascular • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Multiple Myeloma • Oncology • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease • Transplantation • CD34 • CXCL12 • CXCR4

GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol. (PubMed, PLoS One) - P2 | "Co-treatment with CXCL12 and the β2AR agonist epinephrine synergistically increases β-arrestin recruitment to CXCR4 and calcium flux. Addition of propranolol to the G-CSF and GPC-100 combination resulted in greater stem cell mobilization than the G-CSF and plerixafor combination. Together, our studies suggest that the combination of GPC-100 and propranolol is a novel strategy for stem cell mobilization and support the current clinical trial in multiple myeloma registered as NCT05561751 at www.clinicaltrials.gov."

Journal • Preclinical • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34 • CXCL12

GPCR Therapeutics Announces Publication on Improving Hematopoietic Stem Cell Mobilization Using Propranolol with GPC-100 (GlobeNewswire) - "GPCR Therapeutics, Inc...announces publication of a research paper...The paper shows that the company’s lead small molecule asset, GPC-100, a novel CXCR4 antagonist and a potent hematopoietic stem cell (HSC) mobilizer, when combined with the beta-adrenergic receptor blocker propranolol, results in a significant increase in circulating HSCs in mice. These findings strongly support the use of this combination for peripheral blood HSC harvest in autologous stem cell transplant treatment in hematological cancers....The authors highlight that GPC-100 alone shows greater mobilization efficacy than a drug already approved for stem cell mobilization."

Preclinical • Hematological Malignancies

GPCR Therapeutics Announces Publication in Nature Scientific Reports on Novel Anticancer Therapy (GlobeNewswire) - "The paper is entitled ‘Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration.’....The team, led by Professor Won-Ki Huh, shows that another GPCR known as histamine receptor H1 (HRH1) is widely expressed in various cancer cell lines and cancer tissues, and that the level of co-expression of CXCR4 and HRH1 is related to poor prognosis in breast cancer patients. The simultaneous expression of both receptors leads to the formation of CXCR4-HRH1 heteromer, and this complex demonstrates enhanced signalling and migration capabilities...These findings suggest the interaction of CXCR4 and HRH1 may play an important role in cancer progression, thus serving as a potential therapeutic target for anticancer therapy....GPCR recently announced the launch of a US phase 2 trial of GPC-100 in combination with Propranolol for stem cell mobilization in patients with multiple myeloma "

Preclinical • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Pharmacokinetics and Pharmacodynamics of Burixafor Hydrobromide (GPC-100), a Novel C-X-C Chemokine Receptor 4 Antagonist and Mobilizer of Hematopoietic Stem/Progenitor Cells, in Mice and Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "At maximal levels, the CD34 cell counts increased 3- to 14-fold from baseline levels. These results provide support for continued clinical development of burixafor."

Clinical • Journal • PK/PD data • Preclinical • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation • CD133 • CD34 • CXCL12

Identification of core therapeutic targets for Monkeypox virus and repurposing potential of drugs against them: An in silico approach. (PubMed, Comput Biol Med) - "The common inhibitors, i.e., batefenterol, burixafor and eluxadoline were further validated by molecular dynamics simulation to identify their best potential binding modes. The affinity of these inhibitors suggests their repurposing potential. This work can encourage further experimental validation for possible therapeutic management of mpox."

Journal • Infectious Disease

Ph2, Study to Assess the Safety and Efficacy of GPC 100 and Propranolol With and Without G-CSF for the Mobilization of Stem Cells in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: GPCR Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

GPC-100 Is a Novel CXCR4 Inhibitor That Leads to Improved in Vitro Potency and In Vivo Efficacy in Stem Cell Mobilization When Combined with a Beta-Blocker (ASH 2022) - "Previous studies indicate that stress hormones like epinephrine and norepinephrine exert stimulatory effects on cancer progression by modulating tumorigenesis, proliferation, and metastasis via B2AR signaling...Propranolol improved mobilization induced by a single administration of both GPC-100 and AMD3100...Additionally, combination treatment with G-CSF, GPC-100 and Pro may prove to be best-in-class mobilization therapy for ASCT in MM patients, especially those that fail to mobilize with standard of care. As a result, we will initiate a 2 arm, Phase 2 clinical trial evaluating both GPC-100 + Pro, and the triple combination of G-CSF + GPC-100 + Pro in Q4 of 2022."

Preclinical • Bone Marrow Transplantation • Breast Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • Transplantation • CD34 • CXCL12 • CXCR4 • KIT

Ph2, Study to Assess the Safety and Efficacy of GPC 100 and Propranolol With and Without G-CSF for the Mobilization of Stem Cells in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: GPCR Therapeutics, Inc.

New P2 trial • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation