作者: Hassanshahi, Gholamhossein ; Falak, Reza ; Khoshmirsafa, Majid ; Bagherzadeh, Kowsar ; Rahimi, Ali ; Safari, Elaheh ; Karimi, Milad ; Khorramdelazad, Hossein ; Mohammadi, Mahdi ; Darehkordi, Ali

Chemotherapeutic treatment of colorectal cancer (CRC) has not been satisfactory until now; therefore, the discovery of more efficient medications is of great significance. Based on available knowledge, the CXCL12/CXCR4 axis plays a significant role in tumorigenesis, and inhibition of CXCR4 chemokine receptor with AMD3100 is one of the most known therapeutic modalities in cancer therapy. Herein, N, N''-thiocarbonylbis(N'-(3,4-dimethylphenyl)-2,2,2-trifluoroacetimidamide) (A1) was synthesized as a potent CXCR4 inhibitor. A1 inhibitory activity was first evaluated employing Molecular Docking simulations in comparison with the most potent CXCR4 inhibitors. Then, the antiproliferative and cytotoxic effect of A1 on CT26 mouse CRC cells was investigated by MTT assay technique and compared with those of the control molecule, AMD3100. The impact of the target compounds IC₅₀ on apoptosis, cell cycle arrest, and CXCR4 expression was determined by flow cytometry technique. Our finding demonstrated that A1 induces a cytotoxic effect on CT26 cells at 60 μg/mL concentration within 72 h and provokes cell apoptosis and G2/M cell cycle arrest in comparison with the untreated cells, while AMD3100 did not show a cytotoxic effect up to 800 μg/mL dose. The obtained results show that A1 (at a concentration of 40 μg/mL) significantly reduced the proliferation of CT26 cells treated with 100 ng/mL of CXCL12 in 72 h. Moreover, treatment with 60 μg/mL of A1 and 100 ng/mL of CXCL12 for 72 h significantly decreased the number of cells expressing the CXCR4 receptor compared to the control group treated with CXCL12. Eventually, the obtained results indicate that A1, as a dual-function fluorinated small molecule, may benefit CRC treatment through inhibition of CXCR4 and exert a cytotoxic effect on tumor cells.Communicated by Ramaswamy H. Sarma.

2024-11-01·Journal of Biomolecular Structure and Dynamics

Identification of CXCR4 inhibitors as a key therapeutic small molecule in renal fibrosis

Article

作者: N, Kishore ; Gupta, Krishna Kant ; G, Senthil Kumar ; Elumalai, Elakkiya

The final stage of almost all chronic kidney diseases is renal fibrosis. Simple wounds or persistent inflammation can cause tissue inflammation, which, in the case of the kidney, results in scarring. Vascular sclerosis, tubulointerstitial fibrosis and glomerular fibrosis are all types of kidney fibrosis. Renal damage and fibrosis are caused by elevated expression of CXCR4. This study aimed to identify possible pharmacological agents which could bind to and inhibit isoform I of CXCR4 and determine their strength of interactions. The I-TASSER, Galaxyweb and Robetta were used to predict and refine the structure of the CXCR4 protein. ModBase was used to improve the loops, and then the quality was evaluated by using the ERRAT value (92.15) and Ramachandran plot. The improved 3D structure was subjected to small molecule database docking using Maestro (from Schrodinger) and the glide module. GROMACS was used to simulate molecules with the three top low glide scores and the best ADME properties. The best glide score was achieved by ligand ID 4990 (-11.5). Simulations, free energy landscape and residue decomposition analysis revealed that 4990 interacted more consistently with CXCR4 than the other two small molecules.Communicated by Ramaswamy H. Sarma.

2024-09-03·Journal of Clinical Investigation

Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases

Article

作者: Leung, Thomas H ; Jones, Parker ; Prouty, Stephen M. ; Seykora, John T. ; Murphy, Christina ; Leung, Denis H ; Jain, Vaibhav ; Huang, Jianhe ; Leung, Denis H. ; Ahart, Olivia ; Sati, Satish ; Kersh, Anna E ; Kersh, Anna E. ; Hedberg, Matthew L ; Prouty, Stephen M ; Seykora, John T ; Gregory, Simon G. ; Rosenbach, Misha ; Leung, Thomas H. ; Gregory, Simon G ; Hedberg, Matthew L.

Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.

项与 CXCR4 inhibitors(Alpha-9 Theranostics) 相关的新闻（医药）

2024-11-05

·PRNewswire

BioLineRx Announces Oral Presentation on Data from Phase 1 Clinical Trial Evaluating Motixafortide for CD34+ Hematopoietic Stem Cell Mobilization for Gene Therapies in Sickle Cell Disease at ASH 2024

- 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

临床结果临床1期上市批准ASH会议细胞疗法

2024-05-24

·PRNewswire

BioLineRx Announces Abstract on Pilot Study Data from Phase 2 Combination Clinical Trial Evaluating Motixafortide in First-Line Pancreatic Cancer (PDAC) at American Society of Clinical Oncology (ASCO) 2024 Annual Meeting

New analysis of biopsy samples demonstrated a significant increase in CD8+ T-cell density in tumors from all 11 patients treated 7 of 11 patients in the pilot phase experienced a partial response, with 6 confirmed; 10 of 11 patients experienced disease control Poster Presentation on Saturday, June 1, 2024 in Chicago, Illinois TEL AVIV, Israel, May 24, 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 new data from the single-arm pilot phase of the investigator-initiated, randomized CheMo4METPANC Phase 2 combination clinical trial was accepted for presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31-June 4, 2024 in Chicago, Illinois. The CheMo4METPANC trial is evaluating the company's CXCR4 inhibitor motixafortide, the PD-1 inhibitor cemiplimab, and standard-of-care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC). Updated results of the pilot study portion of the Phase 2 study include a new analysis of paired pre- and on-treatment biopsy samples that demonstrated an increase in CD8+ T-cell density in tumors from all 11 patients treated with the combination of motixafortide, cemiplimab and standard-of-care chemotherapies gemcitabine and nab-paclitaxel (P = 0.007). As of February 6, 2024, 7 patients achieved partial response (64%), including 6 confirmed partial responses, and 10 patients (91%) had disease control compared to historic partial response and disease control rates of 23% and 48%, respectively, with gemcitabine and nab-paclitaxel. Preliminary median progression-free survival (PFS) was 9.6 months compared to historic median PFS of 5.5 months with gemcitabine and nab-paclitaxel. "We continue to be encouraged by the data from the pilot phase of this ongoing Phase 2 study, including the initial efficacy results, as well as new findings that the combination therapy including motixafortide demonstrated increased CD8+ T-cell density in the tumors of all patients treated," said Philip Serlin, Chief Executive Officer of BioLineRx Ltd. "The biopsy sample findings continue to confirm immune cell activation and tumor microenvironment modulation observed in previous clinical evaluation. We look forward to our continued collaboration with Columbia University on this clinical research, and to advancing a potential new therapeutic option for pancreatic cancer, which is urgently needed for this difficult-to-treat disease." Based on the encouraging results from the pilot phase of the study, the CheMo4METPANC Phase 2 trial was amended to become a randomized study, with planned enrollment increasing from 30 to 108 patients. Sponsored by Columbia University, the trial is the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies. Poster Presentation at ASCO 2024 McCormick Place, Chicago, Illinois Poster Session Details Primary Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic and Hepatobiliary Title: CheMo4METPANC: A randomized phase 2 study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) compared to chemotherapy alone in metastatic treatment-naïve pancreatic adenocarcinoma Presenter: Gulam Abbas Manji, MD, PhD, Columbia University Herbert Irving Comprehensive Cancer Center Abstract: TPS4208 (see abstract) Poster # 174a Date: Saturday, June 1, 2024 Time: 1:30 PM CDT Location: Hall A About CheMo4METPANC Phase 2 Clinical Trial The multi-center CheMo4METPANC Phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT04543071) is a randomized, investigator-initiated clinical trial in first line metastatic pancreatic cancer. Sponsored by Columbia University, and supported equally by BioLineRx and Regeneron, the study is evaluating the combination of CXCR4 inhibitor motixafortide, PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in 108 patients. The trial's primary endpoint is progression free survival (PFS). Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival. About Pancreatic Cancer Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. In the United States in 2024, an estimated 66,000 adults will be diagnosed with the disease, which accounts for approximately 3% of all cancers in the U.S. and about 7% of all cancer deaths.1 Worldwide, an estimated 496,000 people were diagnosed with the disease in 2020. In the U.S., if the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year relative survival rate is 44%. About 12% of people are initially diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year relative survival rate is 15%. For the 52% of patients who are initially diagnosed with metastatic cancer, the 5-year relative survival rate is 3%.2 In particular, hepatic (liver) metastases are a critical risk factor driving poor prognoses for patients with metastatic PDAC. These data highlight the need for the development of new therapeutic options. About Motixafortide in Cancer Immunotherapy Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. Among CXCR4-expressing immune cells, some exhibit anti-tumoral activity, such as effector T cells and some exhibit pro-tumoral activity and support tumor growth. By blocking the CXCR4 receptor, motixafortide was shown in a Phase 2 study in pancreatic cancer patients to enhance anti-tumoral activity and to ameliorate the pro-tumoral activities by modulating the effector/suppressor cell ratio towards a proinflammatory profile. About BioLineRx BioLineRx Ltd. (NASDAQ/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, expectations with regard to clinical trials of motixafortide. 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. American Cancer Society. Key Statistics for Pancreatic Cancer. Atlanta, Ga: American Cancer Society; 2024. ASCO Cancer.Net. Cancer.Net Editorial Board Approval March 2023. CONTACTS: UNITED STATES John Lacey, BioLineRx [email protected] ISRAEL Moran Meir, LifeSci Advisors, LLC [email protected] ©BioLineRx USA, Inc. 2024. All Rights Reserved. SOURCE BioLineRx

临床结果临床2期免疫疗法ASCO会议上市批准

2024-02-28

·PRNewswire

BioLineRx Announces First Patient Dosed in Randomized Phase 2 Combination Clinical Trial Evaluating Motixafortide in First-Line Pancreatic Cancer (PDAC)

- Conducted in Collaboration with Columbia University, the CheMo4METPANC Phase 2 trial is the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies compared to chemo alone - - Gulam Manji, MD, PhD, of Columbia University to present encore pilot phase data at the Immuno-Oncology (IO) 360° Summit on February 29 - TEL AVIV, Israel, Feb. 28, 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 the first patient has been dosed in the randomized CheMo4METPANC Phase 2 combination clinical trial evaluating the company's CXCR4 inhibitor motixafortide, the PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC). The investigator-initiated trial is being conducted in collaboration with Columbia University and is the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies. "Pancreatic ductal adenocarcinoma (PDAC) has had limited responses to traditional immunotherapy, resulting in a poor prognosis for patients and an urgent need for new treatment approaches," said Philip Serlin, Chief Executive Officer of BioLineRx. "We are encouraged by our early pilot data and look forward to continuing to advance the expanded, randomized Phase 2 CheMo4METPANC trial for patients living with this cancer." Findings from the single-arm pilot phase of the CheMo4METPANC trial will be shared by Dr. Manji at the 10th Annual Immuno-Oncology (IO) 360° Summit in Brooklyn, New York on Thursday, February 29, 2024. The findings were previously presented during an oral presentation at the American Association of Cancer Research (AACR) Special Conference on Pancreatic Cancer in Boston, Massachusetts, September 28, 2023. As of July 2023, 7 of the 11 patients (64%) in the pilot phase experienced a partial response (PR) of which 5 (45%) were confirmed PRs at the time of the data cut; one patient experienced resolution of the hepatic (liver) metastatic lesion; and three patients (27%) experienced stable disease, resulting in a disease control rate of 91%. Motixafortide, BioLineRx's lead therapeutic candidate, was approved by the U.S. Food & Drug Administration (FDA) in September 2023, in combination with filgrastim (G-CSF), to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma, under the brand name APHEXDA®. Motixafortide is also being evaluated in a Phase 1 clinical trial evaluating motixafortide as a monotherapy and in combination with natalizumab for CD34+ hematopoietic stem cell (HSC) mobilization for gene therapies in sickle cell disease (SCD). About CheMo4METPANC Phase 2 Clinical Trial The multi-center CheMo4METPANC Phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT04543071) is a randomized, investigator-initiated clinical trial in first line metastatic pancreatic cancer. Sponsored by Columbia University, and supported equally by BioLineRx and Regeneron, the study is evaluating the combination of CXCR4 inhibitor motixafortide, PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in 108 patients. The trial's primary endpoint is progression free survival (PFS). Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival. About Pancreatic Cancer Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. In the United States in 2024, an estimated 66,000 adults will be diagnosed with the disease, which accounts for approximately 3% of all cancers in the U.S. and about 7% of all cancer deaths.1 Worldwide, an estimated 496,000 people were diagnosed with the disease in 2020. In the U.S., if the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year relative survival rate is 44%. About 12% of people are initially diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year relative survival rate is 15%. For the 52% of patients who are initially diagnosed with metastatic cancer, the 5-year relative survival rate is 3%.2 In particular, hepatic (liver) metastases are a critical risk factor driving poor prognoses for patients with metastatic PDAC. These data highlight the need for the development of new therapeutic options. About Motixafortide in Cancer Immunotherapy Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. Among CXCR4-expressing immune cells, some exhibit anti-tumoral activity, such as effector T cells and some exhibit pro-tumoral activity and support tumor growth. By blocking the CXCR4 receptor, motixafortide was shown in a Phase 2 study in pancreatic cancer patients to enhance anti-tumoral activity and to ameliorate the pro-tumoral activities by modulating the effector/suppressor cell ratio towards a proinflammatory profile. 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 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; whether early stage clinical trial results, or pre-clinical results, will be predictive of, or repeatable in, later clinical trials; 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; 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 22, 2023. 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. American Cancer Society. Key Statistics for Pancreatic Cancer. Atlanta, Ga: American Cancer Society; 2024. ASCO Cancer.Net. Editorial Board Approval March 2023. Contacts: United States John Lacey BioLineRx [email protected] Israel Moran Meir LifeSci Advisors, LLC [email protected] Logo - SOURCE BioLineRx Ltd.

100 项与 CXCR4 inhibitors(Alpha-9 Theranostics) 相关的药物交易

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