Brainstorm Cell Therapeutics(BCLI) - 2024 Q3 - Quarterly Report

Clinical Trials and Regulatory Status - NurOwn® has completed Phase 3 ALS and Phase 2 PMS clinical trials, with positive top-line data announced on March 24, 2021, for PMS[90]. - The FDA granted Fast Track designation and Orphan Drug status for NurOwn® for ALS, indicating its potential significance in treating this condition[93]. - On September 27, 2023, the Advisory Committee voted 17 no, 1 yes, and 1 abstention, stating that NurOwn® did not demonstrate substantial evidence of effectiveness for mild to moderate ALS[90]. - The BLA for NurOwn® was withdrawn on November 3, 2023, in coordination with the FDA, viewed as a withdrawal without prejudice[90]. - A Special Protocol Assessment (SPA) request for a planned Phase 3b clinical trial of NurOwn® was submitted to the FDA on February 23, 2024, and agreement was received on April 9, 2024[95][97]. - The company has reached alignment with the FDA on Chemistry, Manufacturing, and Controls (CMC) aspects of the Phase 3b clinical trial for NurOwn®[102]. - The FDA granted a meeting to discuss the regulatory path forward for NurOwn® on December 6, 2023, focusing on a planned Phase 3b registrational trial[114]. - The FDA granted written agreement on the design for a Phase 3b trial of NurOwn® on April 9, 2024, validating the clinical trial protocol and statistical analysis[140]. - The company plans to submit a Special Protocol Assessment (SPA) request for a Phase 3b clinical trial of NurOwn® for ALS, with the goal of securing FDA agreement on the trial design[150]. Clinical Data and Efficacy - The Phase 2 U.S. study showed a responder analysis of 32.6% for NurOwn® versus 27.7% for placebo, but did not reach statistical significance (p=0.453)[129]. - In a pre-specified subgroup with ALSFRS-R baseline score of 35 or greater, NurOwn® showed a 34.6% responder rate compared to 15.6% for placebo (p=0.305)[131]. - The average change in ALSFRS-R total score from baseline to Week 28 was -1.56 for NurOwn® versus -3.65 for placebo, indicating a statistically significant improvement (p=0.050)[131]. - The Phase 3 trial enrolled rapidly progressing ALS patients, but did not achieve statistically significant results despite showing numerical improvements[128]. - Clinical data from Phase 1/2 trials indicated a slower rate of disease progression post-treatment, as measured by ALSFRS-R and Forced Vital Capacity[117]. - The treatment effects were more pronounced in the rapid progressor subgroup, with significant increases in neurotrophic factors and reductions in inflammatory markers observed post-treatment[124]. - NurOwn® treatment outcomes can be predicted by baseline ALS function and key CSF biomarkers, showing decreases in neuroinflammatory and neurodegenerative markers in treated participants compared to placebo[134]. - A statistically significant treatment difference of more than 2 points (p=0.050) was observed in the average change from baseline in ALSFRS-R for participants with a baseline score of at least 35[135]. - The company presented new biomarker data suggesting that ALS patients may benefit from longer-term treatment with NurOwn® at the 3rd Annual ALS Drug Development Summit[187]. Financial Performance and Funding - For the three months ended September 30, 2024, the company incurred operating costs and expenses of approximately $3,048,000, a decrease of 49.5$6,035,000 for the same period in 2023[201]. - Research and development expenditures, net for the three months ended September 30, 2024 were $1,045,000, a decrease of 68.6$3,330,000 for the same period in 2023[202]. - General and administrative expenses for the three months ended September 30, 2024 were $2,003,000, a decrease of 25.9$2,705,000 for the same period in 2023[205]. - Net loss for the three months ended September 30, 2024 was $2,708,000, compared to a net loss of$1,226,000 for the same period in 2023, resulting in a net loss per share of $0.51[209]. - Net loss for the nine months ended September 30, 2024 was$8,650,000, an improvement compared to a net loss of $11,614,000 for the same period in 2023, with a net loss per share of$1.80[210]. - Cash provided by financing activities for the nine months ended September 30, 2024, was $6,909,000 from sales of common stock under the August 9, 2021 ATM program and June 2024 sales of unregistered securities[218]. - The Company anticipates needing to raise substantial additional financing to fund operations, including conducting a Phase 3b trial for NurOwn®[228]. - The Company has entered into multiple funding alternatives, including public and private sales of Common Stock and warrants, to meet its capital needs[213]. - The Company may not be able to continue as a going concern if it cannot raise additional capital[215]. - Net cash used in operating activities for the nine months ended September 30, 2024, was$8,045,000, primarily due to clinical trial costs, rent, payroll, and legal expenses[217]. Legal Matters - Five lawsuits were filed in the U.S. District Court for the Southern District of New York by purported shareholders between November 1, 2023, and April 12, 2024[237]. - A Securities Complaint was filed against the Company alleging violations related to NurOwn® for the treatment of ALS, seeking damages for an allegedly inflated stock price between February 18, 2020, and September 27, 2023[238]. - The Derivative Complaints assert state law claims for breach of fiduciary duty and unjust enrichment against certain officers and directors, relating to the same issues as the Securities Complaint[239]. - The Company intends to vigorously defend against the lawsuits filed against it[240]. Company Operations and Strategy - The company currently employs 29 employees across the United States and Israel, with a focus on recruiting and retaining talent to support its objectives[94]. - A Memorandum of Understanding (MOU) was entered into with Pluri Inc. for the manufacturing of NurOwn® for the planned Phase 3b trial[106]. - The company is actively exploring the next steps for NurOwn®, including publication of emerging clinical data and development of a protocol for an additional clinical study[90]. - The proprietary technology of NurOwn® involves a multi-step process that includes harvesting stem cells from the patient's bone marrow and administering MSC-NTF cells intrathecally[108]. - The company has optimized its manufacturing capabilities for NurOwn® by leveraging partnerships and operational resources, including a GMP-certified cleanroom facility[144]. - A partnership with Catalent for manufacturing commercial quantities of NurOwn® was established, with successful technology transfer completed by December 7, 2021[145]. - The company is actively engaged in research and development for clinical applications of NurOwn® and MSC-NTF derived exosomes in various neurodegenerative disorders and ARDS[189]. - The company is focused on developing and optimizing large-scale cell culture processes for MSC-NTF exosomes, which may have clinical potential for treating ARDS[190]. - The company aims to advance NurOwn® as a treatment for Alzheimer's Disease, focusing on its capability to target multiple biological pathways[166]. - The company has established a broad portfolio of 27 granted patents and 23 patent applications globally to protect its proprietary technologies[171]. - The company has received patents for NurOwn® in multiple jurisdictions, including the United States, Canada, Japan, Europe, Hong Kong, Brazil, and Israel[185].