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

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)...Ongoing investigations include cumulative daratumumab and IMiD exposure, financial and resource analyses, further observation of poor mobilizers with pCD34 of 1-2 cells/ m L, and evaluation of post-transplant engraftment. Disease Focus of Abstract:Other Other: Apheresis and Cell Manufacturing"

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

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 | "Clinical Trial Registration Number: NCT04543071 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Checkpoint block • Checkpoint inhibition • Clinical • Metastases • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

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

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

Comparative Analysis of Dexamethasone-Enhanced Pre-Medication in Motixafortide-Induced Hematopoietic Stem Cell Mobilization for Multiple Myeloma: A Retrospective Study (ASH 2024) - "Our first 3 patients received the recommended premedication protocol which is oral doses of diphenhydramine 25 to 50 mg, famotidine 20 mg, montelukast 10 mg, and acetaminophen 650 mg, approximately 60 minutes before injection. Patients also received loratadine 10 mg daily beginning on the day of G-CSF initiation, 3 days prior to motixafortide...Subsequently, 16 patients were started on MF-DEX, which consisted of starting famotidine 20 mg, montelukast 10 mg on the day of growth factor administration and continuing until 1 day after collection (5 days total), along with IV dexamethasone 8 mg added onto the standard premedications listed previously...Although patients who received the standard premedications had no grade 4 events and all AEs were manageable with supportive care, it was a clear burden to our patients and nursing staff. After adoption of MF-DEX our center has seen less hypersensitivity reactions and patient outcomes have improved."

Retrospective data • Bone Marrow Transplantation • Dermatology • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Pruritus • Urticaria • CD34

Motixafortide (CXCR4 Inhibition) Alone and in Combination with Natalizumab (VLA-4 Inhibition) As a Novel Regimen to Mobilize Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease: A First-in-Human, Proof-of-Principle Safety and Feasibility Study (ASH 2024) - "G-CSF mobilization is unsafe in SCD, while CXCR4 inhibition (CXCR4i) with plerixafor (P) alone requires multiple mobilization attempts and often yields suboptimal HSC numbers. In those with prior P mobilization, M and N+M enabled 2.8- and 3.2-fold greater HSC mobilization, respectively. Immunophenotypic and transcriptional profiling of CD34+ HSCs mobilized with P, M and N+M is ongoing but preliminary data suggest increased mobilization of primitive HSCs, MPP/CMPs and CLPs; decreased pDCPs; and upregulated expression of CXCR4 and CLP-associated genes with N+M vs CXCR4i alone."

Clinical • Combination therapy • Gene therapy • P1 data • Dermatology • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Pruritus • Sickle Cell Disease • Urticaria • CD34 • CXCR4

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 primary completion date: Aug 2024 ➔ Apr 2025

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

BioLineRx and Ayrmid Ltd. Enter into Exclusive License Agreement to Commercialize APHEXDA (motixafortide) through Gamida Cell Ltd. (PRNewswire) - "BioLineRx Ltd...today announced that on November 20, 2024, the companies entered into a license agreement for motixafortide...Under the terms of the agreement, BioLineRx granted Ayrmid an exclusive license to develop and commercialize APHEXDA (motixafortide) across all indications, excluding solid tumor indications, and in all territories other than Asia. BioLineRx previously granted an exclusive license agreement to Gloria Biosciences for APHEXDA (motixafortide) in the Asia region. In exchange for the license, BioLineRx will receive a $10 million upfront payment and is also eligible to receive up to an additional $87 million of potential commercial milestones, plus royalties ranging from 18% to 23% on net sales of APHEXDA...BioLineRx also entered into a share purchase agreement for a $9 million equity investment from certain funds managed by Highbridge Capital Management, LLC."

Financing • Licensing / partnership • Hematological Malignancies • Multiple Myeloma • Oncology

BioLineRx Reports Third Quarter 2024 Financial Results and Provides Update on Transformation to Drive Shareholder Value (PRNewswire) - "Motixafortide - Pancreatic Ductal Adenocarcinoma (mPDAC): Continued enrollment in the CheMo4METPANC Phase 2b clinical trial collaboration with Columbia University. In addition to Columbia, patient enrollment has begun at Brown University, and three additional sites are anticipated to begin enrollment over the next two quarters. Full enrollment in the randomized trial targeting 108 patients is anticipated in 2027, with a prespecified interim futility analysis planned when 40% of PFS events are observed. Multiple Myeloma: Collaboration partner Gloria Biosciences' stem cell mobilization bridging study IND was filed and approved by the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate initiation of pivotal clinical trial in 1H 2025; Gloria Biosciences has received regulatory approval to commercialize APHEXDA in the Boao Region of China and Macao, areas in Asia that do not require a bridging study."

Enrollment status • New trial • Multiple Myeloma • Pancreatic Ductal Adenocarcinoma

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 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology • CD34

BioLineRx Announces USPTO Allowance of New Composition of Matter Patent on Motixafortide (PRNewswire) - "BioLineRx Ltd...announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for a patent, titled, 'COMPOSITION OF BL-8040,' which covers the composition of motixafortide (APHEXDA/BL-8040). The patent strengthens BioLineRx's robust intellectual property (IP) estate and extends its patent protection on motixafortide in the U.S. through December 2041."

Patent • Multiple Myeloma

SCD Stem Cell Mobilization and Apheresis Using Motixafortide (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Phase IIa Study Evaluating Safety and Efficacy of BL-8040 in Relapsed/Refractory AML Patients (clinicaltrials.gov) - P2 | N=42 | Completed | Sponsor: BioLineRx, Ltd. | Phase classification: P2a ➔ P2

Phase classification • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CXCR4 as a therapeutic target in acute myeloid leukemia. (PubMed, Leukemia) - "Additionally, we explore clinical implications, including prognosis, correlation with WBC count, blast count in the bone marrow and peripheral blood, as well as its association with FLT3-ITD, NPM1 mutations, and FAB classification. Finally, this paper extensively discusses drugs that specifically target the CXCL12-CXCR4 axis, including plerixafor/AMD3100, ulocuplumab, peptide E5, and motixafortide, shedding light on their potential therapeutic value in the treatment of AML."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CXCL12 • CXCR4 • FLT3 • NPM1