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

Motixafortide + G-CSF hematopoietic stem cell mobilization in patients with multiple myeloma following quadruplet induction therapy (ASH 2025) - P1, P3 | "All patients received"enhanced" premeds with: loratadine (10 mg, PO), famotidine (20 mg, PO) and montelukast (10 mg, PO)daily on Day 1-5; plus acetaminophen (975mg, PO), hydrocortisone (200 mg, IV), diphenhydramine (25mg, IV) and famotidine (20 mg, IV) on Day 4 (30-45 mins pre-M). Meanwhile,enhanced premeds were associated with a low rate of AEs relative to standard premeds. Ongoingextended immunophenotyping may shed insight into the mechanism of impaired HSC mobilization post-quad induction, possibly via targeted depletion of a large population of CD38+ HSCs within the CD34+graft."

Clinical • Dermatology • Hematological Malignancies • Multiple Myeloma • Pruritus • CD34

Motixafortide (CXCR4 inhibition) alone and in combination with natalizumab (VLA-4 inhibition) to mobilize hematopoietic stem cells for gene therapy in sickle cell disease: A first-in-human, safety and feasibility study (ASH 2025) - P1 | "G-CSF is unsafe inSCD and the CXCR4 inhibitor (CXCR4i) plerixafor (P) does not reliably yield optimal HSC numbers. Remarkably, HSC transplant of non-SCD marrow into SCD mice (myeloablative cKit-ADCconditioning) reverted the enhanced mobilization phenotype in SCD mice to that of non-SCD mice,indicating enhanced CXCR4i-based mobilization in SCD may track with the hematopoietic system.In conclusion, our first-in-human trial demonstrates the potential of M and N+M as novel G-CSF-freeregimens to safely optimize HSC mobilization in SCD (median CD34+ cells/μl: P=73, M=189, N+M=312).Correlative FC and scRNA seq highlight regimen-specific mobilization of unique HSC subsets, includingincreased CLPs, ERPs and MEPs with N+M. Further mechanistic study of HSC mobilization biology maybuild upon our finding that Townes SCD mice and SCD humans share an enhanced mobilizationphenotype with CXCR4i +/- VLA4i."

Clinical • Combination therapy • First-in-human • Gene therapy • P1 data • Dermatology • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Pruritus • Sickle Cell Disease • Urticaria • 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 hematopoietic progenitor cells in patients with multiple myeloma (ASH 2025) - P2 | "Mediantimes to neutrophil and platelet engraftment were 11 days (range 11-17 days) and 15 days (range 11-27days), respectively.ConclusionsBurixafor, in combination with propranolol and G-CSF, demonstrated an excellent safety profile andeffectively mobilized sufficient HPCs for AHCT, including patients previously treated with lenalidomideand daratumumab. Notably, burixafor enabled same-day administration with leukapheresis, offering akey advantage over other CXCR4 inhibitors, such as plerixafor and motixafortide through its rapidmobilization kinetics. Its favorable safety profile, characterized by minimal adverse events, supporting itspotential clinical utility."

Clinical • IO biomarker • P2 data • Cardiovascular • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypotension • Multiple Myeloma • Musculoskeletal Diseases • Musculoskeletal Pain • CD34 • CXCR4

EMU-116: An oral CXCR4 antagonist as mobilizer of stem and immune cells in normal, neutropenic and sickle cell mice. (ASH 2025) - "The use of CXCR4 antagonists as cell mobilization agents has resulted in 3 FDA approved drugs for use inhematopoietic stem cell transplantation (Plerixafor, Motixafortide) and for treating neutropenia(Mavorixafor). In Swiss mice, EMU-116 dosed orally providesenhanced responses to cyclophosphamide indicating a potential use in chemotherapy-inducedneutropenia. In sickle cell mice, EMU-116 boosts LSKs when dosed orally and could possibly be utilizedfor a future in vivo gene therapy setting with superior effects to Plerixafor."

Immune cell • Preclinical • Bone Marrow Transplantation • Chemotherapy-Induced Neutropenia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease

Efficacy of motixafortide plus G-CSF versus plerixafor plus G-CSF for stem cell mobilization and collection in multiple myeloma: A single-center comparative analysis and interim Results from a prospective study in poor mobilizers (ASH 2025) - "At our institution, a real-world analysis (30MM patients per cohort) compared G-CSF plus motixafortide (prospectively) against G-CSF plusplerixafor (retrospectively, matched by age, gender, race, and IMiD/daratumumab exposure).There were no significant differences in overall mobilization, collection, or apheresis outcomes.Subgroup analysis suggested that patients with low peripheral blood CD34+ counts (pbCD34 ≤5/μL on Day 4 of G-CSF) may achieve a greater rise in CD34+ counts after motixafortide, raisingthe hypothesis that it may benefit "poor mobilizers."We initiated a prospective study to characterize motixafortide efficacy in poor mobilizers(defined as pbCD34+ ≤ 2/μL after 4 days of G-CSF). Full analysis including individual apheresis yields and total collection outcomesis in process. These data will inform future risk-benefit assessments of motixafortide use and helpoptimize treatment regimens in MM patients who mobilize poorly to initial G-CSF doses."

Clinical • Hematological Malignancies • Multiple Myeloma • CD34 • CXCR4

Improved hematopoietic stem cell mobilization for gene therapy using single agent motixafortide in sickle cell disease (ASH 2025) - P1 | "Currently, HSC mobilizationfor SCD is limited to single agent plerixafor (P), a CXCR4 antagonist, since G-CSF is associated with anincreased risk of vaso-occlusive events (VOEs) and death...The median total number of CD34+ cellscollected/day with P was 2.6 x 106/kg compared to 6.8 x 106/kg with M. M was used first line in 3 patientswith preexisting clinical concerns precluding multiple collection cycles...To mitigate known local injection site and potential systemicreactions to M, all patients received prophylactic H-1 and H-2 antagonists and acetaminophen, with 82%receiving additional montelukast...Ongoing clinical trials of M in SCD are examining safety, mobilization efficacy,optimal dose timing, and editing potential (NCT06442761; NCT05618301). Additional studies arewarranted to determine the ideal prophylactic medication regimen."

Gene therapy • Dermatology • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Pruritus • Sickle Cell Disease • Urticaria • CD34

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 | Recruiting | Sponsor: Emory University | Not yet recruiting ➔ Recruiting

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

Clinical Updates (PRNewswire) - "Continued to advance preparations for initiation of a Phase 1/2a clinical trial of GLIX1 in recurrent and newly diagnosed glioblastoma in the first quarter of 2026....Enrollment continues in the CheMo4METPANC Phase 2b clinical trial, which is being led by Columbia University, and supported by both Regeneron and BioLineRx. The CheMo4METPANC trial is evaluating motixafortide in combination with the PD-1 inhibitor cemiplimab and standard chemotherapy (gemcitabine and nab-paclitaxel)."

Enrollment status • New P1/2 trial • Glioblastoma • Pancreatic Ductal Adenocarcinoma

Cellular Therapy and HSCT Mobilizers – Motixafortide (ASH 2023) - No abstract available

Bone Marrow Transplantation

Novel Small Molecule VLA-4 Inhibitors Optimized for Extended Hematopoietic and Progenitor Cell Mobilization (ASH 2023) - "Importantly, a synergistic effect on HSPC mobilization was achieved when WU-106 was co-administered with CXCR4 inhibitors (Plerixafor or BL-8040). We have developed novel, potent PEGylated small molecule VLA-4 inhibitors that have excellent aqueous solubility and pharmacokinetics. The kinetics and magnitude of HSPC mobilization by our PEGylated inhibitors are superior to other previously described VLA-4 inhibitors and an antibody to alpha-4(anti-CD49d)."

Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CXCR4 • ITGA4 • VCAM1

Prolonged CXCR4 Receptor Occupancy By Motixafortide Following a Single Subcutaneous Injection Is Associated with Extended Mobilization of CD34+ Cells in Peripheral Blood for > 24 Hours (ASH 2023) - P1, P3 | "In vitro studies demonstrated complete receptor occupancy by motix starting at a concentration of 3nM. Increasing concentrations resulted in longer duration of receptor occupancy. Mobilization of CD34+ cells to PB was observed within 2 hours after motix injection (1."

Hematological Malignancies • Multiple Myeloma • Oncology • CD34 • CXCL12 • CXCR4

Use of Combination Premedication Prior to Motixafortide Administration Reduced Severity and Frequency of AEs in the Phase 3 Genesis Trial - a Single Center Analysis (ASH 2023) - "Motixafortide was safe and well tolerated with no episodes of anaphylaxis, no Grade 4 AEs and no deaths. Following implementation of a protocol amendment using combination pre-medication with an antihistamine H1 blocker, an H2 blocker, a leukotriene inhibitor and acetaminophen, the frequency and severity of hypersensitivity and injection site AEs associated with motixafortide were markedly improved."

Clinical • P3 data • Dermatology • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Pruritus • Urticaria • CD34

APHEXDA (motixafortide): Learn about this new FDA approved treatment option (ASH 2023) - "Sponsored by BioLineRx, Inc."

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

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

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 • Transplantation • CD34 • CXCR4

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 • 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 • First-in-human • Gene therapy • P1 data • Dermatology • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Pruritus • Sickle Cell Disease • Urticaria • CD34 • CXCR4

Single-Cell MRD Profiling in AML Identifies CXCR4 Expression as a Predictor of Motixafortide Response: An Exploratory Analysis from the BLAST Trial (DGHO 2025) - P2 | "Background: The BLAST trial (NCT02502968) assessed adding the CXCR4 inhibitor Motixafortide to high dose cytarabine consolidation in AML patients in first complete remission (CR). While the BLAST trial showed no overall difference in RFS, single-cell MRD analysis revealed differential treatment effects according to CXCR4 expression. These findings suggest that CXCR4 may serve as a biomarker for response to Motixafortide and highlight the potential of single-cell profiling to inform patient stratification."

Acute Myelogenous Leukemia • CXCL12 • CXCR4

BKT140 Old and new infectious enemies in pregnancy (FIGO 2025) - "FIGO Committee on Infections During Pregnancy"

Infectious Disease

Comparative Analysis of Motixafortide versus Plerixafor for Stem Cell Mobilization and Collection in Multiple Myeloma: A Single Center Real-world Experience (IMS 2025) - "Cohorts were matched by age, gender, race, and prior exposure to daratumumab and IMiDs (lenalidomide/pomalidomide)...Premedication for motixafortide included cetirizine, famotidine, montelukast, acetaminophen, prednisone, and lidocaine cream with ice during a 1-hour monitoring period... In this real-world evaluation, motixafortide did not demonstrate superiority over plerixafor in pCD34 mobilization, stem cell yield, or collection efficiency in MM patients. Higher rates of adverse reactions with motixafortide influenced continued institutional preference for plerixafor in initial ASCT mobilization. Further studies will focus on motixafortide's role in poor mobilizers and post-transplant engraftment."

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

SCD Stem Cell Mobilization and Apheresis Using Motixafortide (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Jul 2026 ➔ Jul 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2028

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

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