Successful autologous hematopoietic stem cell transplant (ASCT) requires a sufficient number of stem cells from peripheral blood to be collected. In many cases, stem cell collection may be difficult due to a number of patient characteristics including age, presence of cytopenias and radiation exposure among other factors. To address problematic collection, the Genesis trial was launched. The Phase III study sought to determine the efficacy of motixafortide and G-CSF combination therapy with G-CSF alone for the mobilization of hematopoietic stem cells.
The primary endpoint of mobilizing more than 6 x 106 CD34+ cells per kg in two apheresis sessions was achieved by 92.5% of subjects in the motixafortide arm compared with 26.2% in the G-CSF arm. The results for patients that presented complicating factors was even more stark between the two arms. Below we provide a comparison of patients with risk factors for poor mobilization who reached collection targets in one apheresis session:
Extended Mobilization of CD34+ Cells
BioLineRx conducted a study to measure in-vitro receptor occupancy, clinical pharmacokinetics and pharmacodynamics of peripheral blood CD34+ cells after motixafortide administration. The assessment was conducted in healthy volunteers and in patients with multiple myeloma. Further aims of the study were to assess associations between apheresis timing and apheresis yield.
The study observed that complete CXCR4 receptor occupancy by motixafortide was observed starting at concentrations as low as 3 nanomolar (nM), with increasing concentrations generating longer receptor occupancy of over 72 hours. Further findings from an examination demonstrated that there was no correlation between the timing of the apheresis procedure and the yield of CD34+ cells within the recommended collection window.
Poster conclusions identified high CXCR4 receptor affinity and slow dissociation rate of motixafortide which result in long receptor occupancy leading to an extended pharmacodynamic effect. CD34+ cells are rapidly mobilized after motixafortide injection, and peak from 12 – 16 hours post administration. 86.3% of patients were able to collect over 6 x 106 CD34+ cells per kilogram in one leukapheresis session. Despite the peak at 12 – 16 hours, there was no correlation between timing of apheresis and cell yield in the 10-hour to 16-hour timepoint following motixafortide injection. The extended pharmacodynamic effect of motixafortide may enable a flexible administration window that allows for leukapheresis to be performed more than 24 hours post administration.
Milestones
➢ Motixafortide, Phase II (Columbia) PDAC study data release – 2023
➢ Presentation of GENESIS data at medical meetings & conferences – 2023
➢ Data published for Phase II PDAC trial – 2H:23
➢ Motixafortide, Phase I launch in Sickle Cell Disease – 2H:23
➢ Motixafortide in SCM target action (PDUFA) date – September 2023
➢ US launch of motixafortide in SCM – 3Q:23
➢ Gloria Biosciences strategic equity investment – October 2023
➢ Approval of Asia Licensing Agreement (Gloria) by Israeli Innovation Authority – 4Q:23
➢ ASH poster presentation: Aphexda in Transplant Centers – December 10, 2023
➢ Start of Gloria Biosciences’ stem cell mobilization bridge study – 2024
➢ Start of Gloria Biosciences’ 1st line pancreatic cancer study (motixafortide & zimberelimab) - 2024
➢ Launch motixafortide and anti-PD-1 combination study - 2024
➢ Potential initiation of randomized Phase 2 study of AGI-134 – 2024
➢ Sickle Cell Disease Phase I readout – 2H:24
Summary
BioLineRx presented two posters in San Antonio, Texas at the tandem transplant conferences ASTCT and CIBMTR. The posters provided additional analysis of the Genesis trial and other data which evaluated the use of motixafortide in multiple myeloma patients and healthy volunteers that required an autologous stem cell transplant. The research found that motixafortide was able to produce a high proportion of stem cells especially in patients with risk factors that may otherwise limit collection. A second study was able to show that motixafortide produces durable receptor occupancy at relatively low concentrations of drug which allow for collection over a multi-hour period post motixafortide administration.
While the data provide additional supportive data for motixafortide, the drug’s ability to safely and effectively collect sufficient cells for stem cell transplantation in multiple myeloma patients has been recognized by the FDA, resulting in the product’s approval. BioLineRx is now commercializing motixafortide branded as Aphexda in the United States.
We maintain our valuation of $7.60 per share which recognizes BioLineRx’ commercialization success around the globe for motixafortide in stem cell collection and in various cancer indications.
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1. BioLineRx Poster Presentation. Motixafortide Enables Consistent, Robust Hematopoietic Stem Cell Collection (HSC) across Populations with In-creased Impaired HSC Mobilization: A Sub-Group Analysis of the Genesis Study. Transplantation & Cellular Therapy Meetings of ASTCT & CIBMTR. February, 2024.
2. BioLineRx Poster Presentation. 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. Transplantation & Cellular Therapy Meetings of ASTCT & CIBMTR. February, 2024.
3. BioLineRx September 2023 Corporate Presentation.
