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Phase III trial of NurOwn shows evidence of mechanism of action in amyotrophic lateral sclerosis.- BrainStorm Cell Therapeutics
BrainStorm Cell Therapeutics announced the presentation of new biomarker analyses supporting the therapeutic benefit of NurOwn in amyotrophic lateral sclerosis (ALS) at the ongoing 5th Annual ALS ONE Research Symposium.
The presentation was delivered by Dr. Stacy Lindborg, Chief Development Officer at Brainstorm, and entitled, "The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells)."
NurOwn's Phase III trial is a strong outlier compared to other late-stage ALS trials due to the inclusion of participants with more advanced disease. The average ALSFRS-R score in NurOwn's Phase III trial was 31, 5 points lower than the registrational trial for the most recently FDA-approved therapy. The inclusion of more advanced participants impacts the assessment of all clinical endpoints based on the ALSFRS-R, as a result of the inability to measure ongoing clinical decline with scale in these participants (i.e., a floor effect). To draw valid conclusions from clinical endpoint data collected in the trial, the floor effect must be addressed. As previously announced, a NurOwn treatment effect was observed in participants in a pre-specified subgroup with less advanced disease (ALSFRS-R baseline score of at least 35) across two endpoints: the primary endpoint (clinical responder analysis) and a key secondary endpoint (average change from baseline to the end of the trial). The difference between NurOwn and placebo for this key secondary endpoint was nominally statistically significant (p=0.050).
An analysis was performed to evaluate the effects of NurOwn and placebo on cerebrospinal fluid (CSF) biomarkers across pathways important to ALS of neuroinflammation, neurodegeneration and neuroprotection. Additional goals were to understand the role that baseline ALSFRS-R values plays on biomarker trajectories and to understand the predictive power of biomarkers on clinical outcomes. As observed in earlier trials, NurOwn was shown to decrease biomarkers associated with neuroinflammation and neurodegeneration, and increase neuroprotective biomarkers over 20 weeks, demonstrating its multifaceted mechanism of action. New analyses looked at the trajectory of biomarkers for the subgroups of participants with baseline ALSFRS-R scores >25 and less than or equal to 25, those most likely to be impacted by the floor effect of the scale. Decreases in neuroinflammatory and neurodegenerative markers and increases in neuroprotective markers in NurOwn treated participants compared to placebo were observed in both subgroups. These results indicate that NurOwn had similar biological effects on ALS participants regardless of the level of disease progression at baseline. Further statistical modeling pre-specified prior to unblinding of the data identified three biomarkers that were predictive of clinical outcomes: baseline LAP, baseline neurofilament light (NfL) and mean change in Galectin-1. These biomarkers relate to neuroinflammatory, neurodegenerative, and neuroprotective pathways, respectively.
Hard to imagine BCLI not being a slam dunk for approval even without the outstanding Biomarker data. I'm leaning more and more to BLA acceptance, Accelerated Review with NO Advisor Panel meeting.
BrainStorm Presents New Biomarker Analyses from NurOwn's Phase 3 ALS Trial at the ALS ONE Research Symposium
https://finance.yahoo.com/news/brainstorm-presents-biomarker-analyses-nurowns-160000968.html
NurOwn® drove biomarker responses, affecting pathways related to neurodegeneration, neuroinflammation, and neuroprotection, that were consistent in participants with both advanced ALS and less advanced disease, confirming the importance of accounting for ALSFRS-R floor effects when evaluating clinical endpoints
NEW YORK, Oct. 7, 2022 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced the presentation of new biomarker analyses supporting the therapeutic benefit of NurOwn® in amyotrophic lateral sclerosis (ALS) at the ongoing 5th Annual ALS ONE Research Symposium. The presentation was delivered by Dr. Stacy Lindborg, Chief Development Officer at Brainstorm, and entitled, "The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells)."
"The new biomarker analyses presented today provide further evidence of NurOwn's multifaceted mechanism of action and show consistent patterns in study participants regardless of the level of disease progression at baseline," said Dr. Stacy Lindborg, Chief Development Officer at Brainstorm. "This compelling finding confirms the importance of accounting for ALSFRS-R floor effects when evaluating clinical endpoints in our phase 3 trial and may further validate the results of subgroup analyses on clinical endpoints in our Phase 3 study which minimize the ALSFRS-R floor. When the subgroup of participants above 26 are analyzed, 2 points of function are preserved on average across 28 weeks in participants treated with NurOwn compared to placebo (p<.05). Moreover, statistical modeling identified biomarkers that have the potential to predict clinical response to NurOwn observed in the trial, with markers of neuroinflammation, neurodegeneration, and neuroprotection selected in the final model. Novel therapies that simultaneously target multiple pathways may offer great potential in the treatment of ALS and highlights the advantages that may come with NurOwn's ability to simultaneously modulate multiple biological pathways."
Presentation Highlights
NurOwn Phase 3 Trial Patient Population and Clinical Outcomes
NurOwn's Phase 3 trial is a strong outlier compared to other late-stage ALS trials due to the inclusion of participants with more advanced disease. The average ALSFRS-R score in NurOwn's Phase 3 trial was 31, 5 points lower than the registrational trial for the most recently FDA-approved therapy. The inclusion of more advanced participants impacts the assessment of all clinical endpoints based on the ALSFRS-R, as a result of the inability to measure ongoing clinical decline with scale in these participants (i.e., a floor effect). To draw valid conclusions from clinical endpoint data collected in the trial, the floor effect must be addressed.
As previously announced, a NurOwn treatment effect was observed in participants in a pre-specified subgroup with less advanced disease (ALSFRS-R baseline score of ≥35) across two endpoints: the primary endpoint (clinical responder analysis) and a key secondary endpoint (average change from baseline to the end of the trial). The difference between NurOwn and placebo for this key secondary endpoint was nominally statistically significant (p=0.050).
Biomarker Data
An analysis was performed to evaluate the effects of NurOwn and placebo on cerebrospinal fluid (CSF) biomarkers across pathways important to ALS of neuroinflammation, neurodegeneration and neuroprotection. Additional goals were to understand the role that baseline ALSFRS-R values plays on biomarker trajectories and to understand the predictive power of biomarkers on clinical outcomes.
As observed in earlier trials, NurOwn was shown to decrease biomarkers associated with neuroinflammation and neurodegeneration, and increase neuroprotective biomarkers over 20 weeks, demonstrating its multifaceted mechanism of action.
New analyses looked at the trajectory of biomarkers for the subgroups of participants with baseline ALSFRS-R scores >25 and ≤25, those most likely to be impacted by the floor effect of the scale. Decreases in neuroinflammatory and neurodegenerative markers and increases in neuroprotective markers in NurOwn treated participants compared to placebo were observed in both subgroups. These results indicate that NurOwn had similar biological effects on ALS participants regardless of the level of disease progression at baseline.
Further statistical modeling pre-specified prior to unblinding of the data identified three biomarkers that were predictive of clinical outcomes: baseline LAP, baseline neurofilament light (NfL) and mean change in Galectin-1. These biomarkers relate to neuroinflammatory, neurodegenerative, and neuroprotective pathways, respectively.
Chaim Lebovits, Chief Executive Officer of Brainstorm commented, "We are grateful to ALS ONE for the opportunity to present these important new data on NurOwn. The biomarker data and statistical analyses further our understanding of NurOwn's mechanism of action and therapeutic potential."
A copy of the of Dr. Lindborg's presentation is available here and on the Events & Presentation page of Brainstorm's corporate website. A replay of Dr. Lindbog's recorded presentation will be available on the Events & Presentation page as of 12pm U.S. EST on Wednesday, October 12, 2022.
Phase 3 NurOwn Study Design
The Phase 3 NurOwn trial was a multi-center, placebo-controlled, randomized, double-blind trial designed to evaluate the safety and efficacy of repeat doses of NurOwn in 189 ALS participants. It was conducted at six centers of excellence: University of California Irvine (Dr. Namita Goyal); Cedars-Sinai Medical Center (Dr. Matthew Burford, Dr. Robert Baloh); California Pacific Medical Center (Prof. Robert Miller, Dr. Jonathan Katz); Massachusetts General Hospital (Prof. Merit Cudkowicz, Dr. James Berry); University of Massachusetts Medical School (Prof. Robert Brown) and Mayo Clinic (Prof. Anthony Windebank, Dr. Nathan Staff). Potential participants with ALS were screened during an 18-week run-in period and those who were rapid progressors (defined as participants with at least a 3-point decrease in ALSFRS-R score during the run-in period) were randomized 1:1 to receive three intrathecal injections (8 weeks between each injection) of NurOwn or placebo. Participants were followed for 28 weeks after treatment. The primary endpoints of the trial were safety assessments and a responder analysis of the rate of decline in ALSFRS-R score over 28 weeks, where response was defined as participants with a 1.25 points/month improvement in the post-treatment versus pre-treatment slope in ALSFRS-R at 28 weeks following the first treatment. Secondary endpoints included the percentage of participants with disease progression halted or improved, ALSFRS-R change from baseline, combined analysis of function and survival, slow vital capacity, tracheostomy-free survival, overall survival and cerebrospinal fluid biomarker measurements. For more information on the trial, visit https://clinicaltrials.gov/ct2/show/NCT03280056.
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 produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.
About BrainStorm Cell Therapeutics Inc.
BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company 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 multiple sclerosis (MS) and was supported by a grant from the National MS Society (NMSS).
Safe-Harbor Statement
Statements in this announcement other than historical data and information, including statements regarding future BLA submission, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect," "likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, BrainStorm's plan to submit a BLA for NurOwn® to the FDA, prospects that the FDA will accept BrainStorm's BLA for NurOwn® for filing and review, prospects that the FDA does not view BrainStorm's NurOwn® product candidate to have demonstrated adequate safety or effectiveness, prospects for future regulatory approval of BrainStorm's NurOwn® treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for BrainStorm's products, if approved, and services, the ability to secure and maintain research institutions to conduct BrainStorm's clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn® treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn® treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, health reform legislation, demand for our services, currency exchange rates and product liability claims and litigation; the impacts of the COVID-19 pandemic and additional strains of COVID-19 or any other health epidemic on our clinical trials, supply chain, and operations; potential delays in any planned or anticipated review or interactions with the FDA due to disruptions at, or inadequate funding of, the FDA; the impact of global economic and political developments on our business, including rising inflation and capital market disruptions; the current conflict in Ukraine, economic sanctions and economic slowdowns or recessions that may result from such development; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. 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.
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SOURCE BrainStorm Cell Therapeutics Inc
More and more analyst are predicting approval. I like the $20+ PPS Target after BLA accepted and approval.
Conclusion
When viewed as a whole, we believe the totality of the evidence shows that NurOwn has a positive treatment effect for ALS patients. In addition, NurOwn has been generally well tolerated in all of its clinical trials with no concerning safety issues identified. Assuming the FDA accepts the BLA for NurOwn, which we believe it will, the agency will be in a similar position that it was in with Relvyrio. We believe there is a high likelihood that the agency will again exert its flexibility and offer the ALS community another treatment option by approving NurOwn. As we await additional information on the BLA filing for NurOwn, our valuation remains at $21 per share.
BCLI: Relvyrio™ Approval Shows FDA Flexibility for ALS Treatments…
https://finance.yahoo.com/news/bcli-relvyrio-approval-shows-fda-100000480.html
Tue, October 4, 2022 at 1:00 PM
By David Bautz, PhD
NASDAQ:BCLI
On September 29, 2022, Amylyx Pharmaceuticals (NASDAQ:AMLX) announced that the U.S. Food and Drug Administration (FDA) had approved Relvyrio™ (formerly AMX0035) for the treatment of amyotrophic lateral sclerosis (ALS). The approval of Relvyrio comes following a circuitous approval pathway that included the FDA advising Amylyx not to seek approval based on results of the company’s Phase 2 clinical trial, an advisory committee meeting in March 2022 in which advisers narrowly voted against recommending approval of the drug, and then a second advisory committee meeting this month in which committee members voted 7-2 to recommend approval.
One of the largest themes to emerge from the approval process for Relvyrio is the flexibility that the FDA can exert given the overwhelming unmet need for ALS patients. Typically, the FDA requires data from at least one robust Phase 3 clinical trial to approve a drug. Relvyrio was approved based on the results of the Phase 2 CENTAUR trial of 137 ALS patients. Results showed that Relvyrio slowed the rate of decline in patients and a post-hoc analysis showed it increased overall survival when compared to those taking placebo. Importantly, Relvyrio was safe and well tolerated, an important threshold that must be met for the FDA to consider approval. Amylyx is currently conducting the Phase 3 PHOENIX trial in ALS, with results expected in 2024.
The approval of Relvyrio shines a light on the difficult position the FDA is in regarding the approval of therapies with uncertain efficacy for diseases such as ALS where the unmet need for new treatments is so high. Dr. Richard Bedlack, the director of the ALS clinic at Duke University, testified at the September advisory committee meeting that the FDA should err on the side of approving a treatment with questionable efficacy, so long as the treatment is safe and generally well-tolerated, for terminal diseases such as ALS rather than waiting for confirmatory evidence of the drug’s efficacy, such as the case with Relvyrio and a Phase 3 readout expected in 2024. He emphasized what a grave mistake it would be to not approve a drug that turns out to have clear clinical benefit that wasn’t obvious at the time of approval.
BrainStorm Cell Therapeutics (NASDAQ:BCLI) will be filing a biologics license application (BLA) for NurOwn® for the treatment of ALS. The company previously conducted two early stage Phase 1/2 and Phase 2 open label clinical trials in Israel and a Phase 2 trial that was conducted at three clinical sites in the U.S. Results from the Phase 2 U.S. trial were published in the journal ‘Neurology’ in December 2019 and showed that in addition to being well-tolerated, NurOwn achieved multiple secondary efficacy endpoints, including higher response rates at all timepoints over 24 weeks. BrainStorm also tested NurOwn in a Phase 3 clinical trial in ALS for which the company announced topline results in November 2020. While the Phase 3 trial did not reach statistical significance on the primary efficacy endpoint, NurOwn treatment was generally well tolerated and there were no new safety concerns identified. A pre-specified subgroup of those early in the course of the disease (ALSFRS-R > 35) showed that 34.6% of NurOwn-treated patients were responders compared to 15.6% on placebo (P=0.288). However, given the wide range of patients enrolled, including many with advanced disease, these results were not replicated for the study as a whole.
In August 2022, an erratum was published in Muscle & Nerve regarding the publication on the Phase 3 clinical trial of NurOwn® for the treatment of ALS. During a routine quality control check and preparations for the upcoming BLA filing, the company discovered an error in the statistical model utilized by the vendor in the analysis of a key secondary endpoint, which was the average change from baseline to week 28 in ALSFRS-R score for the pre-specified subgroup of patients with ALSFRS-R scores at baseline of ≥35 (an indication of less disease progression). Specifically, the original publication reported results for that endpoint using a model that unintentionally deviated from the pre-specified statistical analysis plan by erroneously incorporating interaction terms between the subgroup and treatment. This was the only outcome in which the statistical model was applied incorrectly, thus no other results changed. Applying the correct statistical model for that outcome resulted in the average difference between NurOwn- and placebo-treated patients going from 2.01 points to 2.09 points, but importantly this difference became statistically significant with a P-value of 0.05. In addition, a statistically significant benefit for NurOwn® compared to placebo for that endpoint is also seen for all subgroups with baseline ALSFRS-R scores of at least 26 through the pre-specified subgroup of 35. While the trial did not reach statistical significance on the primary or secondary endpoints, we believe these corrected analyses support the conclusion that NurOwn has a positive treatment effect for patients with ALS.
Conclusion
When viewed as a whole, we believe the totality of the evidence shows that NurOwn has a positive treatment effect for ALS patients. In addition, NurOwn has been generally well tolerated in all of its clinical trials with no concerning safety issues identified. Assuming the FDA accepts the BLA for NurOwn, which we believe it will, the agency will be in a similar position that it was in with Relvyrio. We believe there is a high likelihood that the agency will again exert its flexibility and offer the ALS community another treatment option by approving NurOwn. As we await additional information on the BLA filing for NurOwn, our valuation remains at $21 per share.
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FDA's approval of AMLX's drug is very positive for BCLI IMO. Their data (clinical effect and BioMarker) is much weaker than BCLI and Advocacy for BCLI is Very Strong.
Seeking Alpha: Excellent Summary on BCLI
https://seekingalpha.com/article/4535982-brainstorm-cell-therapeutics-upcoming-bla-in-als
Not weird at all. Just as expected
and predicted in my previous post
which you have probably not read.
AMLX stock is in red territory today on yesterday's news. I would have expected it to shoot up like a rocket. I assumed that the positive AMLX news would provide a halo effect for other companies like Brainstorm (which is currently up 6.71% so far today)...so weird.
See #msg-170077027 and thread.
To your question, i forsee a slight
positive reaction in the range of +5%
Do you think there will be a halo effect with Brainstorm stock tomorrow due to today's AMLX's FDA approval announcement?
My guess is the BLA was filed around the first of September. If I'm correct we'll hear from the FDA by the end of October. FDA acceptance and Priority Review are a slam dunk. It would be surprising for the FDA not to require an Advisory Panel meeting however given the fact that NurOwn provides STATISTICALLY SIGNIFICANT meaningful outcomes as measured by the ALSFRS-R scale in a very important subset of patients (those with early less severe disease) pre-defined in the PIII study, it's not outside the realm of possibilities. BCLI has been able to link positive outcomes with their critical BioMarker data to reinforce NurOwn's mechanism of action which points directly to why it works best in those with early, less severe disease. All IMO
- I just saw this on the No More Excuses ALS Watchdog Group Facebook page:
NurOwn Found Safe, Shows Promise in Phase 2 Trial for Progressive MS
https://multiplesclerosisnewstoday.com/news-posts/2022/09/16/nurown-safe-shows-phase-2-trial-promise-progressive-ms/
BrainStorm Brings MS Data on Heels of ALS BLA Announcement (Updated)
https://www.biospace.com/article/brainstorm-brings-ms-data-on-heels-of-als-bla-submission-announcement-/
Maxim Group analyst Jason McCarthy maintained a Buy rating on Brainstorm Cell Therapeutics (BCLI – Research Report) yesterday and set a price target of $8.00.
BrainStorm Cell Therapeutics Announces Peer Reviewed Publication of Results from the NurOwn® Phase 2 Progressive MS Trial in Multiple Sclerosis Journal
https://finance.yahoo.com/news/brainstorm-cell-therapeutics-announces-peer-100000035.html
Data demonstrate NurOwn's safety and provide preliminary evidence of efficacy in patients with progressive multiple sclerosis
Biomarker analyses show consistent treatment effects in neuroinflammation and neuroprotection pathways
NEW YORK, Sept. 15, 2022 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, today announced the peer reviewed publication of data from the Phase 2 trial of NurOwn in progressive multiple sclerosis (MS) in Multiple Sclerosis Journal. The publication, entitled "Evaluation of neurotrophic factor secreting mesenchymal stem cells in progressive multiple sclerosis", can be found here.
Results from the Phase 2, single-arm, open-label study demonstrated NurOwn's safety and provided preliminary evidence of its efficacy in people with progressive MS. Additionally, biomarker analyses confirmed NurOwn's proposed mechanism of action by showing consistent treatment effects in neuroinflammation and neuroprotection pathways.
Twenty participants were enrolled into the Phase 2 trial, with seventeen receiving all three scheduled NurOwn treatments. The mean age of study participants was 47 years with a mean expanded disability status scale (EDSS) score of 5.4 at screening. Results from the trial were compared to 48 matched control patients who were selected from the from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) registry (Brigham and Women's Hospital and the Ann Romney Center for Neurologic Diseases) at the beginning of the trial.
Treatment with NurOwn resulted in large, clinically meaningful improvements in some patients, as defined by response criteria, across all endpoints measured. These endpoints included timed 25-foot walk speed (T25FW), 9-hole peg test (9HPT), multiple sclerosis walking scale (MSWS), symbol digit modality test (SDMT), and low contrast letter acuity (LCLA). These observed improvements diverged from what was seen in matched patients with progressive MS from the CLIMB registry. Key data from the trial, as well as relevant comparisons to the matched CLIMB registry patients, are shown below.
19% of treated trial participants were responders (as defined by prespecified ≥25% improvement in T25FW or 9HPT at 28 weeks compared to baseline), compared to 4% of the matched CLIMB registry patients.
38% of treated trial participants showed a ≥10-point improvement from baseline in the 12-item MSWS (data for this endpoint were not collected by the CLIMB registry).
27% of treated trial participants showed a ≥8-letter improvement in LCLA binocular at a 2.5% contrast threshold, compared to 6% of the matched CLIMB registry patients.
67% of treated trial participants showed a ≥3-point improvement in the SDMT, compared to 18% of the matched CLIMB registry patients.
47% of treated trial participants showed a ≥8-point improvement in LCLA binocular at a 1.25% contrast threshold (data for this endpoint were not collected by the CLIMB registry).
Across all participants, improvements in function as measured by LCLA, SDMT and MS Functional Composite (MSFC) were observed. Mean improvements from baseline of 3.3 points in the LCLA binocular (2.5% contrast), 3.8 points on the SDMT, and 0.18 points in MSFC were observed in treated trial participants. The corresponding changes in matched CLIMB registry patients estimated at 28 weeks showed declines in function on the LCLA and MSFC. The average change in function decline as measured by T25FW, 9HPT, and EDSS across all treated trial participants demonstrated stabilization of functional decline, with similar or slightly worse findings observed in the matched CLIMB registry patients for the same endpoints.
There were no adverse events related to worsening of MS disease and no clinically significant changes in safety lab results/vital signs, confirming NurOwn's favorable safety profile. Two patients developed symptoms of low back and leg pain, consistent with arachnoiditis, occurring in one of three treatments in both participants.
Treatment also consistently resulted in increases in cerebrospinal fluid neuroprotective factors (VEGF–A, HGF, NCAM-1, Follistatin, LIF and Fetuin–A) and reductions in inflammatory biomarkers (MCP-1, sCD27, SDF-1, and Osteopontin), confirming NurOwn's proposed mechanism of action in progressive MS.
"We were pleased that the study's initial results showed efficacy in patients with progressive MS," said Jeffrey Cohen, M.D., Hazel Prior Hostetler Endowed Chair Professor, Cleveland Clinic Lerner College of Medicine, Director, Experimental Therapeutics, Mellen Center for MS Treatment and Research, and the paper's lead author. "There are both promising biological and preliminary clinical signals of a treatment effect that will require confirmation in a randomized trial."
"There is a high unmet need for better treatments for progressive forms of MS and we congratulate the Brainstorm Cell Therapeutics team for the successful completion and publication of this important study. We look forward to future studies that will help to fully understand the potential of NurOwn and other cell-based therapies for this hard-to-treat form of disease" said Bruce Bebo, EVP Research National MS Society.
Chaim Lebovits, Chief Executive Officer, BrainStorm Cell Therapeutics stated, "Having these data peer reviewed and published in the prestigious Multiple Sclerosis Journal is an important step in the evaluation of NurOwn in progressive MS. We appreciate the expertise and commitment of the study investigators and contributions of study participants to advance our understanding of NurOwn's cellular technology platform. Thanks to their efforts and those of the BrainStorm team, we believe we are closer to providing a meaningful treatment option for those with progressive MS".
Ralph Kern, M.D., MHSc, President and Chief Medical Officer of BrainStorm Cell Therapeutics and co-author of the paper commented, "This publication provides preliminary evidence of NurOwn's potential to modify functional outcomes in progressive MS, which we believe warrants further study. In addition, consistent changes in cerebrospinal fluid neuroinflammation and neuroprotection biomarkers reveal how NurOwn may impact disease mechanisms in progressive MS and are complementary to biomarker results observed in our Phase 3 ALS trial. These observations provide further support for NurOwn as a platform technology with potential broad applications and will bolster BrainStorm's efforts to bring much needed solutions to patients with progressive MS, ALS, and other neurodegenerative diseases."
Study Design
The Phase 2 study (BCT-101) was designed to evaluate the safety, efficacy, and biomarker effects of three intrathecal administrations of NurOwn (MSC-NTF cells), given at two-month intervals, to adults with progressive MS. The trial was conducted at four MS centers of excellence: Cleveland Clinic Mellen Center for MS, Icahn School of Medicine at Mount Sinai, Keck School of Medicine of the University of Southern California, and Stanford University School of Medicine. Twenty participants ages 18-65 with progressive MS were enrolled and 17 received all three treatments and were followed for up to 28 weeks. Participants had baseline EDSS scores of between 3.0 and 6.5, were able to walk 25 feet in 60 seconds or less and had not experienced an MS relapse in the 6 months prior to study enrollment.
The primary efficacy outcome was pre-specified improvement (≥25%) in T25FW or 9-HPT. Additional efficacy endpoints included pre-specified improvements in EDSS, SDMT, LCLA, and MSWS-12. The efficacy outcomes were compared to a pre-specified matched group of progressive MS patients from CLIMB registry (n=48) (Tanuja Chitnis, M.D. Brigham and Women's Hospital and the Ann Romney Center for Neurologic Diseases). The study was sponsored by Brainstorm Cell Therapeutics with additional financial support for biomarker analyses received from the National Multiple Sclerosis Society, Fast-Forward Commercial Research Funding Program. For more information on the trial, visit https://clinicaltrials.gov/ct2/show/NCT03799718.
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 produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.
About BrainStorm Cell Therapeutics Inc.
BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company 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).
Safe-Harbor Statement
Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect," "likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, prospects for future regulatory approval of BrainStorm's NurOwn® treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our products and services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn® treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn® treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation; the impacts of the COVID-19 pandemic on our clinical trials, supply chain, and operations; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. 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
jmullaly@lifesciadvisors.com
Media:
Lisa Guiterman
lisa.guiterman@gmail.com
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View original content:https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-announces-peer-reviewed-publication-of-results-from-the-nurown-phase-2-progressive-ms-trial-in-multiple-sclerosis-journal-301625167.html
SOURCE BrainStorm Cell Therapeutics Inc.
BrainStorm Cell Therapeutics Announces Peer Reviewed Publication of Results from the NurOwn® Phase 2 Progressive MS Trial in Multiple Sclerosis Journal
https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-announces-peer-reviewed-publication-of-results-from-the-nurown-phase-2-progressive-ms-trial-in-multiple-sclerosis-journal-301625167.html
AMLX paves the way for BCLI: 10+ Bagger - Wall Street is asleep on this one.
FDA's Panel nod to AMLX for ALS means FDA acceptance of BCLI's BLA a certainty imo.
The transcript of BCLI's BLA announcement: https://seekingalpha.com/article/4534421-brainstorm-cell-therapeutics-inc-s-bcli-ceo-chaim-lebovits-on-q2-2022-results-earnings-call
Correcting the statistical model for a key Pre-specified Secondary Endpoint resulted in a statistically significant improvement for patients in this sub-group.
This is huge but here's the kicker. The FDA has been putting more emphasis on how ALS treatments affect key Biomarkers. NurOwn improved 3 very important markers in patients who responded favorably. **AND** BCLI will publish this Biomarker data in a PEER REVIEWED JOURNAL in the very near future.
With a Market Cap of $138M, BCLI compared to AMLX Market Cap nearing $2B, it's a 10+ Bagger.
AMLX is up 77% in pre-market and as expected and is pushing up BCLI as well (+10.25% in pre-market). If my guess is right, I would expect to see Brainstorm stock up 20+% by the closing bell today.
I'm really curious to see what their stock price will jump to tomorrow. I assume that it will be similar to Brainstorm stock if they get the same kind of good news.
AMLX FDA 's Positive vote bodes very well for BCLI
AMLX passed the FDA committee vote 7 yes, 2 no, 0 abstain.
I wonder how much that news improves Nurown's odds for FDA approval.
No comparison intended, hence my
semi off topic remark on my post.
Will be interesting to see how the committee interprets this but there's a BIG difference between AMLX and BCLI. AMLX needs to convince the FDA that their new model to evaluate efficacy is solid even though their clinical trial was not designed for it and there's not historical data to support doing so.
BCLI's issue is much different. The vendor in charge of analytical analysis of the trial data made a mistake. Correcting this error resulted in A STATISTICALLY SIGNIFICANT outcome in a KEY SECONDARY ENDPOINT which WAS PRE-SPECIFIED in the trial study designed (no smoke and mirrors). AND many of the BIOMARKERS the FDA believes are important to measure disease showed SIGNIFICANT improvement.
Definitely not Apples to Apples, more like Apples to Dollar bills IMO
FDA still skeptical of ALS drug ahead of high-stakes meeting
Semi O/T)
https://news.yahoo.com/fda-still-skeptical-als-drug-172758215.html
MATTHEW PERRONE
Fri, September 2, 2022 at 8:27 PM·4 min read
WASHINGTON (AP) — Federal health regulators remain unconvinced about the benefits of a closely watched experimental drug for the debilitating illness known as Lou Gehrig’s disease, even as they prepare to give its drugmaker a rare second opportunity to make a public case for the treatment.
Amylyx Pharmaceuticals' experimental drug has become a rallying cause for patients with the deadly neurodegenerative disease, their families and members of Congress who are pushing the FDA to approve the drug.
But regulators said Friday that the drugmaker's new analyses are not “sufficiently independent or persuasive” to establish effectiveness. The agency posted its review ahead of a Wednesday meeting of its outside advisers, who will vote on whether to recommend approval.
In March, the same panel of neurological experts voted 6-4 that the company’s data failed to show a convincing benefit for ALS, or amyotrophic lateral sclerosis. It’s extremely rare for the FDA to call a second review meeting after its advisers have already voted.
The FDA will ask the panel to review several new statistical analyses, which the company says strengthen the case that its drug prolongs life and delays hospitalization and other severe complications. The FDA says the experts can take into account “the unmet need in ALS," the disease's seriousness and other factors specific to the terminal diseases.
Elsewhere in its review the FDA detailed the flexibility it can apply to drug approval decisions, particularly for deadly diseases, which suggests “there is a chance that the FDA is still looking for a way to approve the product,” SVB analyst Marc Goodman wrote in a note to investors. He gives Amylyx a 50% chance of approval.
ALS destroys nerve cells needed to walk, talk, swallow and — eventually — breathe. There is no cure and most people die within three to five years.
The FDA's review reflects some of the biggest questions facing the agency, including: How strict should it be in enforcing approval standards for drugs against rare, fatal diseases? And how much weight, if any, should be given to outside appeals from patients, advocates and their political allies?
Typically, FDA approval requires two large studies or one study with a “very persuasive” effect on survival.
Amylyx’s data comes from one small, mid-stage trial that showed some benefit in slowing the disease, but which was marred by missing data, implementation errors and other problems, according to FDA reviewers.
Amylyx says follow-up data gathered after the study concluded shows the drug extended life. When the company followed patients who continued taking the drug, they survived about 10 months longer than patients who never took the drug, according to a new company analysis.
But FDA said Friday the new approach “suffers from the same interpretability challenges” as Amylyx’s initial study and that the new analysis “is not independent data.”
The FDA does not publicly explain its rationale for holding meetings. But some outside analysts believe the agency is hoping that more external input will strengthen its hand when it renders its final decision, expected by the end of the month.
Amylyx’s drug is a combination of two older drug ingredients: a prescription medication for liver disorders and a dietary supplement associated with traditional Chinese medicine. The Cambridge, Massachusetts, company has patented the combination and says the chemicals work together to shield cells from premature death. Its co-founders first hit upon the combination as Brown University students.
Some ALS patients already take both pills. FDA approval would likely compel insurers to cover the treatment.
The FDA will hear again from patients and advocacy groups, such as I AM ALS, which has lobbied the FDA and Congress for more than two years to make the drug available. The group’s founder, Brian Wallach, said ALS patients, physicians and researchers believe that the company’s data warrants approval.
“Patients do their homework— we know this isn’t going to cure us,” said Wallach, who was diagnosed with ALS in 2017 and spoke through an interpreter. “But we also know it might keep us here until the next drug comes along and that one might be a cure.”
Wallach currently takes the part of Amylyx’s treatment that is available as a dietary supplement.
Despite the negative FDA review, there are several outside developments that could tip the FDA toward approval.
In June, Canadian regulators approved the drug for ALS patients, the first country to do so. That decision puts FDA regulators in a “precarious position,” says bioethicist Holly Fernandez-Lynch.
"They typically like to be out ahead when making approval decisions," said Fernandez-Lynch, who teaches at the University of Pennsylvania. “They like to make the argument that they are not a barrier to patients accessing things that might help them.”
Shares of Amylyx fell more than 23% to close at $18 in trading Friday.
FDA has 60 days to accept or decline BLA submission. I believe we'll know the outcome by the end of October.
Quote from Seeking Alpha.
Conclusion:
Brainstorm has decidedon August 15, 2022 that it would soon file a biologics license application for its autologous stem-cell-based treatment candidate NurOwn in ALS. At first sight, that announcement came as a surprise, as the drug had failed to reach a primary endpoint in ALS. At second sight, it may not. Minor corrections to the initial readout, due to the original publication having reported results that unintentionally deviated from the trial's pre-specified statistical analysis, led the company to report that a prespecified subgroup of patients with a baseline ALSFRS-R score of ≥35 did report statistical benefit. Additionally, this benefit seemingly extends to all patients with scores from 26 to 35.
The FDA’s transcripts on Amylyx’s drug candidate Albriova provide guidance as to the importance of neurofilament light chain as a biomarker. The FDA seems to find this biomarker of significant importance, as it is in part because Amylyx’s Albrovia was unable to demonstrate any change over placebo here, that the FDA’s advisory committee voted against the approval of Albriova. Biogen decided to go for accelerated approval of its drug candidate Tofersen in ALS based on measurements of the same biomarker. NurOwn has shown a 82% reduction of this biomarker over the course of 5 months, which is significantly better than Biogen’s Tofersen.
I believe exciting times are ahead for the ALS space. Brainstorm Cell Therapeutics is now ready to file for a BLA for NurOwn. Amylyx’s Albriova is up for a PDUFA on September 29, 2022. The FDA’s call on Tofersen is slated for January 25, 2023. My bet is that, if any of these would make it to approval, NurOwn actually stands the best chances. But in light of new data, it would have to move the FDA to revise its earlier decision on NurOwn.
For all the above, I am rating Brainstorm Cell Therapeutics as a buy.
Brainstorm Cell Therapeutics: Upcoming BLA In ALS
Aug. 21, 2022 3:57 AM ETBrainstorm Cell Therapeutics Inc. (BCLI)
Summary
Brainstorm Cell Therapeutics is a company developing NurOwn as an autologous stem cell-based treatment for ALS and MS.
NurOwn’s mechanism of action relies on bringing down neuroinflammation and altering glial activity, a recipe that seems to be a winner in neurodegenerative diseases.
After its Phase 3 trial in ALS did not reach its primary endpoint, the company announced on August 15, 2022 that it would still file a BLA in ALS.
Upon reanalysis of the data, statistical significance was in fact found in a predefined subgroup as well as in a larger group of ALS patients.
Like Biogen’s Tofersen but unlike Amylyx’s Albrioza, NurOwn significantly reduces the biomarker Neurofilament Light Chain, which the FDA’s AdCom finds of high value.
On August 15, 2022, Brainstorm Cell Therapeutics (NASDAQ:BCLI) caught the investment community by surprise, announcing that it would file a BLA for ALS. Brainstorm’s NurOwn failed to reach a primary endpoint in its Phase 3 trial in ALS. Yet, corrections to the initial data were reported and an erratum to the initial publication was published. Those corrections, although minor, did mean that statistical significance was shown in a predefined subgroup that had a baseline ALSFRS-R score of ≥35. Additionally, NurOwn also showed benefit in patients with ALSFRS-R scores of at least 26-35. Higher ALSFRS-R score mean less neurodegeneration, meaning NurOwn shows benefit in patients that have not yet reached the final stages of ALS disease.
That was all i could copy/paste
BioSpace: NurOwn A Study in the complexity of ALS trials
https://www.biospace.com/article/nurown-a-study-in-the-complexity-of-als-trials-/
I do hope the treatment will be approved,
for my sake as a shareholder as well as
for all ALS patients, but one has to be
realistic and read the following:
DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.
Notwithstanding: Go NurOwn® Go!
BCLI: Filing a BLA for NurOwn® for the Treatment of ALS…
https://finance.yahoo.com/news/bcli-filing-bla-nurown-treatment-141600304.html
This stood out to me:
Brainstorm Cell Therapeutics (BCLI) Receives a Buy from Maxim Group
https://www.tipranks.com/news/blurbs/brainstorm-cell-therapeutics-bcli-receives-a-buy-from-maxim-group?mod=mw_quote_news
As of 11:08AM EDT. Market open.
3.7477+0.3077 (+8.94%)
Inching up indeed!
Still a long way to go.
Might be the reason for the extra chatter from the company and Maxim.
Shares are up over 26% since 7/1. Convenient.
No More Excuses! ALS Watch Dog Group
Public group
·
13.8K members
----------------------------------------------------------------------------
I just checked in and joined the group!
The only one to decide if and when to
raise funds is the company itself.
I don't have a Facebook account so can someone go to the No More Excuses! ALS Watch Dog Group - Facebook page and put up a posting informing them that Brainstorm is running low on cash and that they should do a fundraising event for Nurown. If the FDA approves the Nurown BLA, No More Excuses can use that money to help Brainstorm get up and running as fast as possible.
Indeed, If the cash burn continues at current rate,
eg ~ $6 million in a single quarter, BCLI will
need to raise capital much sooner than later.
The one thing that I'm wooried about:
I am pretty confident the stock will
start an inching up process the
coming days and weeks!
Brainstorm Cell Therapeutics Inc.'s (BCLI) CEO Chaim Lebovits on Q2 2022 Results - Earnings Call Transcript
https://seekingalpha.com/article/4534421-brainstorm-cell-therapeutics-inc-s-bcli-ceo-chaim-lebovits-on-q2-2022-results-earnings-call?source=content_type%3Aall%7Cfirst_level_url%3Aportfolio%7Csection%3Aportfolio_content_unit%7Csection_asset%3Alatest%7Cline%3A1
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