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- Findings suggest motixafortide alone, and in combination with natalizumab, could support the collection of the large number of stem cells required by gene therapies for sickle cell disease within a single apheresis cycle - - Data from proof-of-concept study shows that motixafortide was safe and well tolerated - - Oral presentation at ASH 2024 on Saturday, December 7, 2024 in San Diego, California - TEL AVIV, Israel and WALTHAM, Mass., Nov. 5, 2024 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, today announced that an abstract including the initial results from a Phase 1 clinical trial evaluating motixafortide as monotherapy and in combination with natalizumab for CD34+ hematopoietic stem cell (HSC) mobilization for gene therapies in sickle cell disease (SCD) was accepted for oral presentation at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, California. The proof-of-concept study, conducted in collaboration with Washington University School of Medicine in St. Louis, is exploring alternative HSC mobilization strategies that could significantly improve the treatment journey of patients with sickle cell disease seeking gene therapy. "Currently available gene therapies for sickle cell disease rely on the collection of significant quantities of CD34+ hematopoietic stem cells, posing challenges for many patients," said Zachary Crees, MD, principal investigator for the trial, Division of Oncology, Washington University School of Medicine. "The findings in this trial suggest that patients with sickle cell disease given motixafortide alone, or in combination with natalizumab, could mobilize and potentially collect the number of stem cells required for approved gene therapies in a single apheresis cycle. These are encouraging findings that we look forward to presenting in greater detail at ASH 2024." "We are encouraged by the initial findings in this Phase 1 study showing that motixafortide is safe and well-tolerated and may hold potential to improve the overall treatment process and access to gene therapy for more people with SCD," said Philip Serlin, Chief Executive Officer of BioLineRx. "We look forward to continued collaboration with Washington University on this important research and our ongoing work to develop motixafortide for the potential benefit of patients with sickle cell disease." The Phase 1 safety and feasibility study is evaluating motixafortide (CXCR4 inhibitor) as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene therapies in SCD. As reported in the abstract, five patients completed mobilization and apheresis with motixafortide alone, and four of five with motixafortide in combination with natalizumab. Motixafortide alone, and in combination with natalizumab, were safe and well-tolerated in the trial. Common adverse events (AEs) were transient and included Grade 1-2 injection site (pruritis, tingling/pain) and systemic reactions (pruritis, hives). No Grade 4 AEs or vaso-occlusive events occurred. Motixafortide alone, and in combination with natalizumab, resulted in robust CD34+ HSC mobilization to peripheral blood (PB). Motixafortide alone mobilized a median of 198 CD34+ cells/μl (range 77-690) to PB with median 3.49x10 CD34+ cells/kg as part of a single blood volume collection, projecting the collection of 13.9x106 HSCs in a normal, single-day four blood volume apheresis collection session. Motixafortide in combination with natalizumab mobilized a median of 231 CD34+ cells/μl (range 117-408), with median 4.64x10 CD34+ cells/kg collected as part of a single blood volume collection, projecting the collection of 18.6x106 CD34+ HSCs in a single day four blood volume apheresis collection session. The two approved gene therapies for sickle cell disease in the U.S. require 16.5 million, and 22 million, total CD34+ HSCs, respectively.i,ii Unfortunately, granulocyte colony-stimulating factor (G-CSF), the most commonly used drug to support the collection of stem cells, is contraindicated in patients with SCD. The use of the mobilization agent plerixafor is the current standard of care for collecting HSCs for SCD gene therapies; however, plerixafor alone requires multiple mobilization attempts and often yields suboptimal HSC numbers. For some, gene therapy may be prohibitive due to the failure to obtain adequate numbers of HSCs. In the trial, patients who underwent prior mobilization with plerixafor, experienced 2.8- fold greater HSC mobilization with motixafortide alone, and 3.2-fold greater HSC mobilization with motixafortide in combination with natalizumab compared to plerixafor. Oral Presentation at ASH 2024 San Diego Convention Center, San Diego, California Oral Presentation Details Session Name: 711. Cell Collection and Manufacturing of HSPCs, CAR-T Cells, and Other Cellular Therapy Products: Innovations in Mobilization, Collection, and Manufacturing for Cellular Therapies Title: 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 Presenter: Zachary D. Crees, MD, Division of Oncology, Washington University School of Medicine, Saint Louis, MO Abstract ID#: 193210 Date: Saturday, December 7, 2024 Time: 12:00 PM Location: San Diego Convention Center, Room 25 About the Clinical Trial of Motixafortide in Sickle Cell Disease (SCD) The trial (ClinicalTrials.gov Identifier: NCT05618301) is a safety and feasibility study to evaluate motixafortide (CXCR4 inhibitor) as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene therapies in SCD. The study enrolled five adults with a diagnosis of SCD who are receiving automated red blood cell exchanges via apheresis. The trial's primary objective is to assess the safety and tolerability of motixafortide alone and the combination of motixafortide + natalizumab in SCD patients, defined by dose-limiting toxicities. Secondary objectives include determining the number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via apheresis; and determining the kinetics of CD34+ HSPC mobilization to peripheral blood in response to motixafortide alone and motixafortide + natalizumab in SCD patients. About Sickle Cell Disease Sickle cell disease (SCD) is one of the most common genetic diseases globally, affecting millions of people throughout the world and disproportionately impacting persons of color. Sickle cell disease arises from mutations in the hemoglobin gene, ultimately leading to the production of abnormally shaped (sickle) red blood cells that tend to stick within blood vessels causing their occlusion. The clinical manifestations of SCD include anemia and blood vessel occlusion which can lead to both acute and chronic pain, as well as tissue ischemia across multiple organ systems (e.g., stroke, heart attack, respiratory failure), ultimately compromising end organ function. The cumulative impact of these complications significantly impacts morbidity and mortality for patients with SCD. About BioLineRx BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX) is a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases. The company's first approved product is APHEXDA® (motixafortide) with an indication in the U.S. for stem cell mobilization for autologous transplantation in multiple myeloma. BioLineRx is advancing a pipeline of investigational medicines for patients with sickle cell disease, pancreatic cancer, and other solid tumors. Headquartered in Israel, and with operations in the U.S., the company is driving innovative therapeutics with end-to-end expertise in development and commercialization, ensuring life-changing discoveries move beyond the bench to the bedside. Learn more about who we are, what we do, and how we do it at , or on Twitter and LinkedIn. Forward Looking Statement Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These include statements regarding management's expectations, beliefs and intentions regarding, among other things, the potential benefits of APHEXDA, the execution of the launch of APHEXDA and the plans and objectives of management for future operations and expectations and commercial potential of motixafortide, as well as its potential investigational uses. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials, and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; whether BioLineRx's collaboration partners will be able to execute on collaboration goals in a timely manner; whether the clinical trial results for APHEXDA will be predictive of real-world results; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates, including the degree and pace of market uptake of APHEXDA for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients; whether access to APHEXDA is achieved in a commercially viable manner and whether APHEXDA receives adequate reimbursement from third-party payors; BioLineRx's ability to establish, operationalize and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for and ability to access sufficient additional financing, including any unexpected costs or delays in the commercial launch of APHEXDA; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; statements as to the impact of the political and security situation in Israel on BioLineRx's business; and the impact of the COVID-19 pandemic, the Russian invasion of Ukraine, the declared war by Israel against Hamas and the military campaigns against Hamas and other terrorist organizations, which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 26, 2024. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law. Contacts: United States John Lacey BioLineRx [email protected] Israel Moran Meir LifeSci Advisors, LLC [email protected] i LYFGENIA Prescribing Information; December 2023. ii CASGEVY Prescribing Information; December 2023. Logo - SOURCE BioLineRx Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Beam Therapeutics gave an initial look at the first handful of patients who received its experimental gene-edited treatment for sickle cell disease. As of July 2, six people with severe sickle cell disease have been dosed with its therapy, which uses base editing to turn on a functioning fetal form of the blood protein hemoglobin, the biotech said Tuesday. One patient in the Phase 1/2 trial died from respiratory failure four months after getting BEAM-101, which was deemed likely related to the busulfan conditioning required to receive the gene-edited therapy. “It was a very sad outcome,” Beam CEO John Evans said in an interview before the data came out. “That reminds us, frankly, of how severely sick these patients are where they’re making the decision to try these curative therapies but that have real risks.” Beam’s shares $BEAM fell 10% Tuesday morning. In the four patients with at least one month of follow-up, Beam reported its therapy induced fetal hemoglobin by greater than 60% and reduced sickle cell hemoglobin by 36% or less, an effect that the company said “was sustained over time.” Evans said the numbers were similar to what was seen in largely asymptomatic sickle trait carriers and higher than what’s been reported for Vertex’s sickle cell therapy Casgevy, which is one of two approved gene therapies for the disease. Beam also reported a median of 17 and 20 days for neutrophil and platelet engraftment, respectively. Evans noted that timeline was shorter than Casgevy’s. “That’s frankly less time in the hospital, less risk of infection,” he said. In Casgevy’s pivotal clinical trial for sickle cell disease, median neutrophil and platelet engraftment time was 27 and 32 days, respectively. By using base editing, Beam believes it is not only able to make a precise single-letter change to the DNA, it is also able to do so in a way that doesn’t require double-stranded breaks, which Evans described as “gentler on the cell.” The data are still too early to determine whether outcomes on Beam’s therapy are meaningfully different than Casgevy and bluebird bio’s Lyfgenia, but Evans pointed to initial signs that he said show “the advantages of that coming out.” Behind Evans’ pitch that Beam’s experimental sickle cell therapy can do better than the approved ones are questions about the commercial appetite for a third gene therapy for sickle cell. Editas Medicine, another player trying to break into the sickle cell therapy market, announced last month that it is pivoting away from its clinical sickle cell therapy and focusing on an in vivo approach. The launches of the first two sickle cell gene therapies — which were approved the same day last year — have taken time. Vertex reported Monday that 40 patients have started the process to receive its therapy, and it made $2 million in revenue from the first patient dosed in the third quarter. Bluebird bio said in late September that it had 41 patient starts across its three gene therapies, though it also announced it was cutting costs and laying off staff at that time. Beam’s data are still very early, but the company said so far no patients experienced extreme bouts of pain called VOCs that are related to sickle cell disease. The biotech also reported that markers of hemolysis — the process by which blood cells break down — either normalized or improved for all patients. Treatment with BEAM-101 is a long process that involves extracting a patients’ blood stem cells and editing them to turn on fetal hemoglobin. Patients receive intense chemotherapy conditioning to clear space in their bone marrow for the new cells, which are then reinfused. The conditioning also comes with a high risk of infertility. Beam’s data were shared in an abstract released as part of the annual ASH meeting, which will take place in December. Beam expects to present data with longer follow-up and from seven patients, and it will also detail additional preclinical results from two monkeys that received an experimental regimen it is developing that aims to do away with the intense conditioning. Stay tuned for more coverage of ASH from Endpoints , and sign up for our virtual ASH event here .