galectin-1

Scientists have created a new zebrafish xenograft platform to screen for novel treatments for an aggressive brain tumor called glioblastoma, according to a new study. Glioblastoma is an aggressive and difficult-to-treat brain tumor in adults. On average, patients survive for only 1.5 years. The standard of care treatment for this disease, which includes surgery followed by radiation and chemotherapy, has not changed in 18 years. That's partly because the cancer is highly variable with many differences across the patient population. Secondly, these cancer cells also deceive the body in insidious ways: they even recruit immune cells called macrophages to help them. And thirdly, they are out of reach for most anti-cancer drugs, which have only a limited capacity to penetrate brain tissues. Besides the standard of care treatment, oncologists try out drugs on glioblastoma patients without any guarantee they'll work, often involving adverse side effects. "These patients really are in need of new therapies," says Professor Holger Gerhardt, the senior author of the study and vice-Scientific Director of the Max Delbrück Center in Berlin. "It is very important to identify the patients who do respond to a specific treatment, and the ones who do not." Lise Finotto, the lead author and a cancer researcher at the VIB-KU Leuven Center for Cancer Biology in Belgium and formerly at the Max Delbrück Center, and her senior collaborators Gerhardt and Professor Frederik De Smet at KU Leuven, have created a screening platform that could be refined to find novel targets for drugs against glioblastoma. It could also be used to check if a particular patient will respond to a therapy. The study was published in "EMBO Molecular Medicine." To understand how macrophages can interact with glioblastoma cells of different patients, the researchers created zebrafish "avatars." Gerhardt's lab works extensively with zebrafish. These three-centimeter-long fish are considered good model organisms as their embryos are translucent, making it possible to monitor what's happening inside. An unexpected survival Finotto investigated glioblastoma stem cells from seven patients collected by scientists at the De Smet lab, which is establishing a living tissue bank of glioblastoma samples. She injected them into zebrafish embryos, creating xenograft models -- an avatar for each specific patient. When she live-imaged the embryos, it appeared that the glioblastoma cells had adapted well to their new environment. She saw the zebrafish's immune system sending macrophages as part of an immune response to control the tumor. But as is typical in glioblastoma, the macrophages were suppressed. The tumors have several mechanisms to reprogram the macrophages so they help them grow. "We wanted to learn how to revert the macrophages to a tumor-attacking state," Finotto says. And a clue surfaced when they noticed that the tumor of one patient did not suppress the normal macrophage response. "Upon closer investigation of the medical details, we discovered that this patient was what we call a 'long-term survivor'," says De Smet at KU Leuven. "It's a term used for glioblastoma patients with a survival of more than five years, which is exceptionally rare in this brain cancer." Testing platform Their curiosity about the patient became the driving force behind the project, Finotto says. When they cultured the tumor cells and macrophages together and did single-cell RNA sequencing, they learned that one gene, LGALS1, was downregulated in the tumor of the long-term survivor compared to the others. Earlier studies have also shown that silencing of LGALS1 in glioblastoma cells can result in longer survival. The scientists confirmed their results by knocking out the gene in another patient's sample and observed in the zebrafish models that the tumor became less invasive. This platform could be used to identify promising targets other than LGALS1 for the treatment of glioblastoma, Finotto says. And with some refinement, zebrafish avatars could be used to identify which treatments will work. Researchers could investigate whether the tumor cells from particular patients grafted into zebrafish respond when treated with various drugs to find the ones that lead to tumor regression, Gerhardt says. "Armed with this information, we could inform oncologist and help them to make more supported treatment decisions for the patient," De Smet says.

NEW YORK, Sept. 27, 2023 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced the outcome of the U.S. Food and Drug Administration's Cellular, Tissue and Gene Therapies Advisory Committee meeting to review the Biologics License Application (BLA) for NurOwn®, an investigational mesenchymal stem cell therapy for the treatment of amyotrophic lateral sclerosis (ALS). Today the Committee voted that NurOwn did not demonstrate substantial evidence of effectiveness for treatment of mild to moderate ALS. "The Committee's vote was a sad outcome for the ALS community, who have too few options to help manage this merciless and deadly disease," said Stacy Lindborg, PhD, co-CEO of BrainStorm. "We firmly believe that the totality of data presented for NurOwn today provide a compelling case for approval, with clinical evidence in those with less advanced disease supported by strong and consistent biomarker data that are predictive of clinical response. We truly did our best to make the NurOwn data clear to the FDA Advisory Committee. Unfortunately, had more time and opportunity been allowed, many remaining questions posed by Advisory Committee members could have been sufficiently addressed." Chaim Lebovits, President and Chief Executive Officer of BrainStorm, added: "The discussion in today's Advisory Committee meeting, and the heartrending testimony of those living with ALS and their loved ones, underscores not only the need for regulatory flexibility but also for continuing research in the field. The people of BrainStorm will do everything in our power to fulfill the obligation we deeply feel we owe to the ALS community, and in the coming weeks we will explore all options available to us." About NurOwn® The NurOwn® technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are harvested from each person with ALS and are manufactured using an innovative and proprietary process to secrete neurotrophic factors to target specific neurodegenerative diseases. The lead program for NurOwn is for the treatment of ALS, which is under FDA review. BrainStorm's long-term commitment to ALS is demonstrated in preclinical research and a series of clinical studies, all of which have been published in peer-reviewed journals. The Phase 3 pivotal trial of NurOwn did not reach statistical significance on the primary or secondary endpoints, likely due to a "floor effect," which confounds measurement of disease progression in patients with more advanced disease. A thorough analysis of NurOwn Phase 3 data shows evidence of clinically meaningful effectiveness in ALS participants who have not progressed to advanced levels of disease progression. In a pre-specified group of participants with an ALSFRS-R score ³35, there was a larger treatment effect across all endpoints with NurOwn compared to placebo, which aligned with historical trials and the study power assumptions and resulted in a statistically significant difference on a key endpoint (change from baseline in ALSFRS-R). Additionally, a post-hoc sensitivity analysis of patients across threshold of >26 through ≥35 on the ALSFRS-R highlighted that NurOwn-treated patients retain, on average, two points of function more compared to placebo–clinically meaningful preservation and important for quality of life for a person living with ALS and their loved ones. NurOwn's clinical program also included most robust cerebrospinal fluid (CSF) biomarker study ever done in ALS, strong and consistent biomarker data, which are predictive of clinical response in the trial, span pathways that are important to ALS (neuroinflammation, neurodegeneration, neuroprotection), and align with NurOwn's mechanism of action. Biomarker data in all trial participants showed consistent biological patterns of NurOwn reducing markers of inflammation and neurodegeneration and increasing neuroprotective markers relative to placebo. Biomarker patterns were consistent across all NurOwn-participants, including in those with Advanced ALS disease where clinical scales, such as the ALS Functional Rating Scale, have demonstrated measurement challenges. Three CSF biomarkers were predictive of clinical outcomes in NurOwn-treated participants–NfL, galectin-1, latency associated peptide of TGF-beta1 (LAP or TGF-b). The NurOwn clinical program has generated valuable insights into the pathology of ALS, as well as disease progression and treatment. Since the initial Phase 3 readout, BrainStorm has shared the full dataset through rigorous peer-reviewed analysis, including: quantification of Floor Effect, which had been noted but never before explored in depth; evaluation of multiple pre-specified biomarkers, collected at seven different points across 20 weeks during the trial, allowing a longitudinal view; and analysis of genetic data, which represents one of the first ALS trials to prospectively invoke pharmacogenomic analysis of clinical outcome, offering great promise for the development of future treatments for ALS. BrainStorm previously announced the FDA's intention to hold an ADCOM meeting to review NurOwn for the treatment of ALS. BrainStorm filed a BLA for NurOwn on September 9, 2022, and received a Refusal to File (RTF) letter from FDA on November 8, 2022. Following a Type A meeting and subsequent discussions with the FDA BrainStorm requested that CBER utilize the FDA's "File Over Protest" procedure, which offers the shortest amount of time to complete the regulatory process. The BLA was filed over protest, allowing completion of the regulatory process in the shortest time possible, and active review resumed on February 7, 2023. About BrainStorm Cell Therapeutics Inc. BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. BrainStorm holds the rights to clinical development and commercialization of the NurOwn® technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive MS and was supported by a grant from the National MS Society (NMSS). Notice Regarding Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties, including statements regarding the upcoming ADCOM meeting related to NurOwn, the timing of a PDUFA action date for the BLA for NurOwn, the clinical development of NurOwn as a therapy for the treatment of ALS, the future availability of NurOwn to patients, and the future success of BrainStorm. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on BrainStorm's current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. These potential risks and uncertainties include, without limitation, management's ability to successfully achieve its goals, BrainStorm's ability to raise additional capital, BrainStorm's ability to continue as a going concern, prospects for future regulatory approval of NurOwn, whether BrainStorm's future interactions with the FDA will have productive outcomes, and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at . These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations, and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. CONTACTS Investor Relations: John Mullaly LifeSci Advisors, LLC Phone: +1 617-429-3548 [email protected] Media: Lisa Guiterman Phone: +1 202-330-3431 [email protected] SOURCE BrainStorm Cell Therapeutics Inc.

FDA advisory committee (ADCOM) meeting to review NurOwn® for ALS NEW YORK, Sept. 27, 2023 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced that Nasdaq has halted trading of the Company's common stock. The U.S. Food and Drug Administration's (FDA) Cellular, Tissue and Gene Therapies Advisory Committee is meeting today to review BrainStorm's Biologics License Application (BLA) for NurOwn® for the treatment of amyotrophic lateral sclerosis (ALS). The ADCOM meeting is scheduled to take place 10:00 am to 6:00 pm ET. The FDA has posted briefing materials, agendas and webcast information for the meeting that can be accessed on the Agency's website here. The online web conference meeting can be viewed through this link. BrainStorm's BLA for NurOwn® has a Prescription Drug User Fee Act (PDUFA) action date targeted to occur by December 8, 2023. About NurOwn® The NurOwn® technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are harvested from each person with ALS and are manufactured using an innovative and proprietary process to secrete neurotrophic factors to target specific neurodegenerative diseases. The lead program for NurOwn® is for the treatment of ALS, which is under FDA review. BrainStorm's long-term commitment to ALS is demonstrated in preclinical research and a series of clinical studies, all of which have been published in peer-reviewed journals. The Phase 3 pivotal trial of NurOwn® did not reach statistical significance on the primary or secondary endpoints, likely due to a "floor effect," which confounds measurement of disease progression in patients with more advanced disease. A thorough analysis of NurOwn® Phase 3 data shows evidence of clinically meaningful effectiveness in ALS participants who have not progressed to advanced levels of disease progression. In a pre-specified group of participants with an ALSFRS-R score ³35, there was a larger treatment effect across all endpoints with NurOwn® compared to placebo, which aligned with historical trials and the study power assumptions and resulted in a statistically significant difference on a key endpoint (change from baseline in ALSFRS-R). Additionally, a post-hoc sensitivity analysis of patients across threshold of >26 through ≥35 on the ALSFRS-R highlighted that NurOwn®-treated patients retain, on average, two points of function more compared to placebo–clinically meaningful preservation and important for quality of life for a person living with ALS and their loved ones. NurOwn®'s clinical program also included the most robust cerebrospinal fluid (CSF) biomarker study ever done in ALS, strong and consistent biomarker data, which are predictive of clinical response in the trial, span pathways that are important to ALS (neuroinflammation, neurodegeneration, neuroprotection), and align with NurOwn®'s mechanism of action. Biomarker data in all trial participants showed consistent biological patterns of NurOwn® reducing markers of inflammation and neurodegeneration and increasing neuroprotective markers relative to placebo. Biomarker patterns were consistent across all NurOwn® participants, including in those with Advanced ALS disease where clinical scales, such as the ALS Functional Rating Scale, have demonstrated measurement challenges. Three CSF biomarkers were predictive of clinical outcomes in NurOwn®-treated participants–NfL, galectin-1, latency associated peptide of TGF-beta1 (LAP or TGF-b). The NurOwn® clinical program has generated valuable insights into the pathology of ALS, as well as disease progression and treatment. Since the initial Phase 3 readout, BrainStorm has shared the full dataset through rigorous peer-reviewed analysis, including: quantification of Floor Effect, which had been noted but never before explored in depth; evaluation of multiple pre-specified biomarkers, collected at seven different points across 20 weeks during the trial, allowing a longitudinal view; and analysis of genetic data, which represents one of the first ALS trials to prospectively invoke pharmacogenomic analysis of clinical outcome, offering great promise for the development of future treatments for ALS. BrainStorm previously announced the FDA's intention to hold an ADCOM meeting to review NurOwn® for the treatment of ALS. BrainStorm filed a BLA for NurOwn® on September 9, 2022, and received a Refusal to File (RTF) letter from FDA on November 8, 2022. Following a Type A meeting and subsequent discussions with the FDA BrainStorm requested that CBER utilize the FDA's "File Over Protest" procedure, which offers the shortest amount of time to complete the regulatory process. The BLA was filed over protest, allowing completion of the regulatory process in the shortest time possible, and active review resumed on February 7, 2023. About BrainStorm Cell Therapeutics Inc. BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. BrainStorm holds the rights to clinical development and commercialization of the NurOwn® technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive MS and was supported by a grant from the National MS Society (NMSS). Notice Regarding Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties, including statements regarding the ADCOM meeting related to NurOwn®, the timing of a PDUFA action date for the BLA for NurOwn®, and the clinical development of NurOwn® as a therapy for the treatment of ALS. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on BrainStorm's current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. These potential risks and uncertainties include, without limitation, management's ability to successfully achieve its goals, BrainStorm's ability to raise additional capital, BrainStorm's ability to continue as a going concern, prospects for future regulatory approval of NurOwn®, whether BrainStorm's future interactions with the FDA will have productive outcomes, and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at . These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations, and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. Logo - CONTACTS Investor Relations: John Mullaly LifeSci Advisors, LLC Phone: +1 617-429-3548 [email protected] Media: Lisa Guiterman Phone: +1 202-330-3431 [email protected] SOURCE BrainStorm Cell Therapeutics Inc.