Aphexda (motixafortide) / BioLineRx, GenFleet Therap, Gloria Pharma, Ayrmid - LARVOL DELTA

BioLineRx Reports Second Quarter 2025 Financial Results… (Yahoo Finance) - "APHEXDA generated sales of $1.7 million in the second quarter of 2025, providing royalty revenue to the Company of $0.3 million."

Sales • Multiple Myeloma

A Pharmacodynamic Study of the Apheresis Product of Multiple Myeloma Patients Undergoing Quad-induction Followed by Motixafortide + G-CSF Mobilization (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial (clinicaltrials.gov) - P4 | N=94 | Not yet recruiting | Sponsor: Emory University

New P4 trial • Allergy • Hematological Malignancies • Multiple Myeloma • Oncology

A Pharmacodynamic Study of the Apheresis Product of Multiple Myeloma Patients Undergoing Quad-induction Followed by Motixafortide + G-CSF Mobilization (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Aug 2025 | Trial primary completion date: Jan 2026 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Evaluating efficacy of Fc-enhanced CTLA-4 inhibitor botensilimab, bastilimab with or without CXCR4 inhibitor (BL-8040) in an orthotopic murine model (ESMO-GI 2025) - "We evaluated the efficacy of using CXCR4 inhibitor (CXCR4i) BL-8040 in combination with Fc enhanced cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor Botensilimab (BOT) and Balstilimab (BAL) in an orthotopic murine PDAC model. We generated orthotopic pancreatic cancer models with KPC cells in C57BL/6 mice. Treatment with BOT/BAL or BOT/BAL/CXCR4i increased CD8+ T-Cells expressing GranzymeB, decreased CD4+ cells, and decreased F4-80+ macrophages that correspond with decreased tumor size."

IO biomarker • Preclinical • Gastrointestinal Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • CD4 • CD8 • CXCL12 • CXCR4 • GZMB • PD-1

Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

CXCR4 EXPRESSION IN AML BLASTS AND ITS IMPACT ON CXCR4 INHIBITOR EFFICACY DURING CONSOLIDATION THERAPY: RESULTS FROM THE SAL BLAST TRIAL (EHA 2025) - P2 | "Background: The BLAST trial (NCT02502968) is a recently completed double- blind, placebo controlled, randomized, multicenter, phase II trial, which evaluated the addition of the CXCR4 inhibitor Motixafortide to high-dose cytarabine consolidation in acute myeloid leukemia (AML) patients in first complete remission (CR). In conclusion, while the BLAST trial showed no overall RFS difference, our single-cell MRD analysis provided insights into CXCR4 inhibition effects. The observed changes in CXCR4 expression in leukemic blasts and NK cells suggest complex interactions within the bone marrow microenvironment. These findings provide new insights into CXCR4 inhibition's complex effects within the bone marrow microenvironment and its potential impact on anti-leukemic immune responses."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CXCR4 • TP53

CheMo4METPANC: Combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) in metastatic treatment-naïve pancreatic adenocarcinoma—Updated clinical and translational findings. (ASCO 2025) - P2 | "Preliminary results from this pilot study of MCGN in mPDAC were promising, with a PR rate of 63% and disease control rate (DCR) of 91%. Based on these results, the study was amended to transition to a randomized phase 2 trial testing MCGN compared to GN (2:1; N = 108). The primary endpoint is PFS."

Checkpoint block • Checkpoint inhibition • Clinical • Metastases • Alopecia • Anemia • Hepatocellular Cancer • Immunology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD8 • CXCL12 • CXCR4

BioLineRx Announces New Pilot Phase Data from Phase 2 Combination Trial of Motixafortide in First-Line Pancreatic Cancer (PDAC) to be Presented at ASCO 2025 Annual Meeting (PRNewswire) - "BioLineRx Ltd...announced that a poster including new data from the single-arm pilot phase of the investigator-initiated, randomized CheMo4METPANC Phase 2 combination clinical trial will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30-June 3, 2025 in Chicago, Illinois....Updated results from the pilot phase indicate that four of eleven patients remained progression free after more than one year....The pilot clinical trial of motixafortide, cemiplimab, gemcitabine and nab-paclitaxel (N=11) demonstrated an overall response rate (ORR) of 64% (7/11) and a disease control rate (DCR) of 91% (10/11), compared to historical ORR and DCR of 23% and 48%, respectively, with gemcitabine and nab-paclitaxel."

P2 data • Pancreatic Ductal Adenocarcinoma

BioLineRx Reports First Quarter 2025 Financial Results and Provides Corporate Update (PRNewswire) - "APHEXDA generated sales of $1.4 million in the first quarter of 2025, providing royalty revenues to the Company of $0.3 million....Additional trial sites were activated for the CheMo4METPANC Phase 2b clinical trial, which is expected to have a positive impact on patient recruitment. Full enrollment in the randomized trial, which is being led by Columbia University, and supported by both Regeneron and BioLineRx, is planned for completion in 2027, with a prespecified interim analysis planned when 40% of progression free survival (PFS) events are observed."

Sales • Trial status • Pancreatic Ductal Adenocarcinoma

Development and Validation of the LC-MS/MS Method and Its Application for Pharmacokinetic Studies for the Simultaneous Estimation of Motixafortide and Filgrastim in rat Plasma. (PubMed, Biomed Chromatogr) - "This method was successfully applied in pharmacokinetic studies, ensuring reliable and accurate quantification of co-administered motixafortide and filgrastim. These findings significantly contribute to optimizing therapeutic protocols and enhancing treatment outcomes for cancer patients."

Journal • PK/PD data • Preclinical • Oncology

Comparative Analysis of Motixafortide versus Plerixafor for Autologous Stem Cell Mobilization and Collection in Multiple Myeloma: A Single Center Real-World Experience (ASGCT 2025) - "These cells are used after high-dose melphalan as autologous stem cell rescue/transplant (ASCT)...Cohorts were matched for age, gender, race, and exposure to daratumumab and lenalidomide/pomalidomide (IMiDs)...Premeds for motixafortide were cetirizine, famotidine, montelukast, acetaminophen, prednisone 20mg, and lidocaine cream, with ice during a 1-hour monitoring period...48% of motixafortide recipients required intervention (additional acetaminophen or famotidine or new administration of methylprednisolone IV, diphenhydramine or ketorolac) for pruritis (45%), tingling/burning or pain (34 and 31%), and erythema/rash or facial flushing (24% each)... This initial real-world evaluation of motixafortide administration on feasibility, safety, and stem cell mobilization in MM patients at a single center (without changes in practice patterns) did not show superiority over plerixafor in pCD34, stem cells collected, or time/days required to target 4x10^6 CD34/kg. Our institution..."

Clinical • Real-world • Real-world evidence • Dermatology • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Pruritus • CD34

MORPHEUS-EC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (clinicaltrials.gov) - P1/2 | N=410 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1 • TIGIT

Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2025 ➔ Jun 2025 | Trial primary completion date: Dec 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Targeting CXCR4: implications for clonal dynamics and MRD assessment in acute myeloid leukemia (ITOC 2025) - P2 | "For our analysis, we used bone marrow samples from a phase II clinical trial (BLAST, NCT02502968) investigating the effect of a novel CXCR4 inhibitor (BL-8040) in combination with conventional consolidation chemotherapy in AML patients in first clinical remission (CR)...Our findings suggest that the role of CXCR4 inhibition in AML treatment may involve multifaceted mechanisms, including effects on leukemic stem cells and possibly other CXCR4-expressing immune cells. Further research is needed to clarify these mechanisms and identify patient subgroups that may benefit from CXCR4 inhibition in AML treatment."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CXCL12 • DNMT3A • NPM1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=341 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Pharmacological aspects of FDA-approved novel drug therapies against cancer in 2023: a comprehensive review. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "About 29% (16 out of 55) of these newly FAD-approved drugs have been prescribed for various cancers such as locally progressed or metastatic breast cancer, relapsed or refractory multiple myeloma, prostate cancer, non-Hodgkin lymphoma, acute myeloid leukemia, and nasopharyngeal carcinoma. This manuscript covering pharmacological aspects such as therapeutic effects, approved dose, mechanisms of action, pharmacokinetics, adverse effects, contraindications, and safety in special cases like pregnant, lactating, pediatric, and geriatric patients of FDA-approved anticancer drugs shall be of immense importance for researchers, academician, oncologists, and cancer patients."

FDA event • Journal • Review • Acute Myelogenous Leukemia • Breast Cancer • Genito-urinary Cancer • Geriatric Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Prostate Cancer • Solid Tumor

Chemo4METPANC Combination Chemokine Inhibitor, Immunotherapy, and Chemotherapy in Pancreatic Adenocarcinoma (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Gulam Manji | Trial completion date: Aug 2025 ➔ Aug 2028 | Trial primary completion date: Jul 2025 ➔ Jun 2028

Checkpoint inhibition • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024. (PubMed, Expert Opin Ther Pat) - "Although the first CXCR4 drug plerixafor emerged over a decade ago (2007), recently the first peptide (motixafortide, 2023) and the first oral small molecule (mavorixafor, 2024) CXCR4 antagonists became FDA approved. In the last five years there has been significant advancement in CXCR4 antagonists as gauged by the FDA approval of two drugs. The search for second and third generation compounds will be the focus of future efforts with new uses and better properties which likely could come from some of the IP described herein."

Journal • Review • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Oncology

Unmet Need in Stem Cell Mobilization for Gene Therapy in Patients with Sickle Cell Disease (SCD): A Multicenter Review (TCT-ASTCT-CIBMTR 2025) - "G-CSF cannot be used in SCD and mobilization with plerixafor (P), typically requires 8-12 weeks of exchange transfusions and a median of 2 collection cycles (multiple aphereses/cycle), increasing the morbidity of the procedure, delaying time to treatment, and increasing the need for multiple central line placements. Motixafortide may be an alternative for HSC mobilization in SCD, however, it has not been evaluated in GT for SCD. Phase 1 trials are underway."

Clinical • Gene therapy • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Sickle Cell Disease • CD34 • CXCR4

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

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Jan 2025 | Trial primary completion date: Oct 2025 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

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

Motixafortide for Hematopoietic Stem and Progenitor Cell Mobilization and Collection in Sickle Cell Disease (ASH 2024) - P1 | "These include a stressed and damaged bone marrow niche, myelosuppression by the most commonly used disease modifying agent hydroxyurea (HU), and inability to mobilize with granulocyte colony stimulating factor (G-CSF). Mobilization of HSCs to the PB using the CXCR4 antagonist plerixafor followed by apheresis collection is the current strategy for harvesting HSCs...Conclusion : HSC mobilization with motixafortide may represent a safe and effective strategy to improve HSC mobilization and collection in individuals with SCD. Information gained by this study may contribute to the medical care, treatment, and advancement of transformative therapy for individuals with SCD."

Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Sickle Cell Disease • CD34