Brainstorm Cell Therapeutics Profile
Brainstorm Cell Therapeutics Inc. (BrainStorm) operates as a biotechnology company.
The company engages in the development and commercialization of best-in-class autologous cellular therapies for the treatment of neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease); Progressive Multiple Sclerosis (PMS); Alzheimer's disease (AD); and other neurodegenerative diseases. NurOwn, the company's proprietary cell therapy platform, leverages cell culture methods to induce autologous bone marrow-derived mesenchymal stem cells (MSCs) to secrete high levels of neurotrophic factors (NTFs), modulate neuroinflammatory and neurodegenerative disease processes, promote neuronal survival, and improve neurological function.
NurOwn has completed its Phase 3 ALS and Phase 2 PMS clinical trials. On November 17, 2020, the company announced top-line data from its Phase 3 ALS trial. On March 24, 2021, the company announced positive top-line data from its Phase 2 trial evaluating three repeated intrathecal administrations of NurOwn, each given 2 months apart, as a treatment for PMS. On June 24, 2020, the company announced a new clinical program focused on the development of NurOwn as a treatment for AD. On August 15, 2022, the company announced its decision to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for NurOwn for the treatment of ALS. On September 9, 2022, the company filed a BLA to the FDA for NurOwn for the treatment of ALS. On November 10, 2022, the company announced that it had received a refusal to file (RTF) letter from the FDA regarding its BLA. The FDA indicated that the company may request a Type A meeting to discuss the content of the RTF letter. On December 12, 2022, the company announced the submission of a Type A meeting request with FDA to discuss the contents of the RTF letter previously issued by the FDA regarding the BLA for NurOwn for the treatment of ALS. On December 27, 2022, it announced that the FDA granted a Type A meeting to discuss the contents of the RTF letter previously issued regarding its BLA for NurOwn for the treatment of ALS. The Type A Meeting was held on January 11, 2023.
BrainStorm was presented with multiple options to return the BLA to regulatory review, which included the regulatory procedure to File over Protest. Additionally, within these discussions, FDA committed to review amendments that were filed to address items raised in the RTF letter. These discussions resulted in BrainStorm requesting the FDA to file the company's BLA over Protest, as this was the regulatory procedure that would allow it to reach an ADCOM in the shortest amount of time. BrainStorm notified the FDA on February 6, 2023 of its decision to request the FDA to file the NurOwn BLA for ALS over Protest. It received confirmation from FDA that the BLA was re-filed on Feb 7, 2023. The company received the FDA Type A meeting minutes on February 9, 2023. It submitted an amendment to its BLA on March 7, 2023, in which it responded to the majority of the items included in the RTF letter. Written feedback was received on March 22, 2023, from the FDA project manager associated with the BLA confirming the FDA's decision to grant an ADCOM for the NurOwn BLA for ALS. On March 27, 2023, the company announced that the FDA will hold an ADCOM to discuss the company's BLA for NurOwn for the treatment of ALS. The BLA for NurOwn to treat ALS is under active review by the FDA.
The company's wholly owned Israeli subsidiary, BrainStorm Cell Therapeutics Ltd. (Israeli Subsidiary), holds exclusive rights to commercialize NurOwn technology through a licensing agreement with Ramot (Ramot), the technology transfer company of Tel Aviv University, Israel.
NurOwn has a strong and comprehensive intellectual property portfolio and was granted Fast Track designation by the FDA and Orphan Drug status by the FDA and the European Medicines Agency (EMA) for ALS.
The company has completed two early stage Phase 1/2 and 2 open-label clinical trials of NurOwn in patients with ALS at the Hadassah Medical Center (Hadassah) in Jerusalem, Israel, as well as a Phase 2 double-blind, placebo-controlled, multicenter clinical trial at three prestigious U.S. Medical centers - the Massachusetts General Hospital (MGH) in Boston, Massachusetts Memorial Hospital in Worcester, Massachusetts, and the Mayo Clinic in Rochester, Minnesota - all highly experienced in the management, investigation, and treatment of ALS.
The first two open-label trials were approved by the Israeli Ministry of Health (MoH). The first-in-human trial, a Phase 1 safety and efficacy trial of NurOwn administered either intramuscularly or intrathecally in 12 ALS patients, was initiated in June 2011. In the Phase 2 dose-escalating study, 14 ALS patients were administered NurOwn by a combined route of intramuscular and intrathecal administration.
The Phase 2 U.S. study was conducted under an FDA Investigational New Drug (IND) application. For this trial, NurOwn was manufactured at the Connell and O'Reilly Cell Manipulation Core Facility at the Dana Farber Cancer Institute in Boston and at the Human Cellular Therapy Lab at the Mayo Clinic.
Following successful completion of the Phase 2 study, the company conducted a Phase 3 trial (a multi-dose double-blind, placebo-controlled, multicenter trial protocol) that was designed to generate data to potentially support a BLA submission in the U.S. for NurOwn in ALS. In October 2019, the clinical trial completed enrollment of an enriched patient population of rapid progressors based on superior outcomes observed in the Phase-2 pre-specified sub-group.
Strategy
A key element of the company's overall strategy is to establish a broad portfolio of patents and other methods to protect its proprietary technologies and products. The company's business strategy is to develop and commercialize NurOwn for the treatment of neurodegenerative diseases.
Intellectual Property
Brainstorm is the sole licensee or assignee of 27 granted patents, and 23 patent applications in the United States, Canada, Europe, Israel, and Brazil, as well as in additional countries worldwide, including countries in the Far East and South America (in calculating the number of granted patents and patent applications, each European patent validated in multiple jurisdictions was counted as a single patent).
On February 18, 2020, the U.S. Patent and Trademark Office (USPTO) issued U.S. Patent No. 10,564,149 titled 'Populations of Mesenchymal Stem Cells That Secrete Neurotrophic Factors'. The allowed claims cover a pharmaceutical composition for MSC-NTF cells secreting neurotrophic factors (NurOwn) comprising a culture medium as a carrier and an isolated population of differentiated bone marrow-derived MSCs that secrete neurotrophic factors.
On June 3, 2020, the European Patent Office (EPO) granted European patent No. 2880151 titled 'Methods of Generating Mesenchymal Stem Cells which secrete Neurotrophic Factors'. The allowed claims cover the method for manufacturing MSC-NTF cells (NurOwn).
On September 1, 2020, the Israeli Patent Office issued Israeli Patent No. 246943 titled 'Method of Qualifying Cells'. The granted claims cover a method of qualifying whether a cell population is a suitable therapeutic for treating Amyotrophic Lateral Sclerosis (ALS) and an isolated population of cells that secrete neurotrophic factors which are qualified useful as a therapeutic for treating ALS.
On September 16, 2020, the company announced that the Japanese Patent Office (JPO) has granted Brainstorm's Japanese Patent No. 6,753,887, titled 'Methods of Generating Mesenchymal Stem Cells Which Secrete Neurotrophic Factors'. The allowed claims cover a method of generating cells which secrete neurotrophic factors from human undifferentiated mesenchymal stem cells (MSCs) derived from the bone marrow of a single donor. The said neurotrophic factors includes brain derived neurotrophic factor (BDNF); glial derived neurotrophic factor (GDNF); hepatocyte growth factor (HGF); and vascular endothelial growth factor (VEGF).
On December 15, 2020, the Canadian Patent office sealed Patent No. 2,937,305 titled 'Pharmaceutical composition comprising bone-marrow derived mesenchymal stem cells'. The granted claims include a pharmaceutical composition for NurOwn (MSC-NTF cells, Mesenchymal Stem Cells secreting Neurotrophic Factors), comprising a culture medium as a carrier and an isolated population of differentiated bone marrow-derived MSCs that secrete neurotrophic factors.
On December 22, 2020, the U.S. Patent and Trademark Office (USPTO) issued U.S. Patent No. 10,869,899 titled 'Isolated cells and populations comprising same for the treatment of CNS diseases'. Granted claims cover an isolated cell population secreting GDNF, a pharmaceutical composition comprising the isolated cells, and a device comprising the pharmaceutical composition, including a device that is adapted for administration of the isolated cell population into the spinal cord.
On February 19, 2021, the Hong Kong patent office sealed Patent No. HK1209453 titled 'Methods of Generating Mesenchymal Stem Cells which secrete Neurotrophic Factors'. Allowed claims cover the method for manufacturing MSC-NTF cells (NurOwn).
On November 30, 2021, the U.S. Patent and Trademark Office (USPTO) issued U.S. Patent No. 11,185,572 titled 'Mesenchymal stem cells for the treatment of CNS diseases'. The granted claims are for a method of treating a disease selected from the group consisting of Parkinson's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, stroke and Huntington's disease using MSC-NTF cells (NurOwn).
On February 15, 2022, the company announced that the Brazilian Patent Office granted patent application BR112015001435-6 titled 'A method of generating cells which secrete Brain Derived Neurotrophic Factor (BDNF), Glial Derived Neurotrophic Factor (GDNF), Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF), wherein said cells do not Secrete Nerve Growth Factor (NGF)'. The granted claims cover a method of manufacturing MSC-NTF cells (NurOwn).
Patents protecting NurOwn have been issued in the United States, Canada, Japan, Europe, Hong Kong, Brazil, and Israel.
Additional PCT patent applications have been filed and National phase applications are under examination in several jurisdictions worldwide. Specifically, International Patent Application WO 2018/015945 was filed on July 17, 2017, and WO/2019/198077 was filed on April 10, 2019.
Trademarks
NurOwn is a registered trademark (application no. 85154891, filed October 18, 2010) for use in connection with 'compositions of cells derived from stem cells for medical purposes; stem cells for medical purposes.' U.S. Trademark No. 4641441 for NurOwn was registered on November 18, 2014.
The NurOwn proprietary technology is fully owned by Brainstorm Cell Therapeutics Ltd., the company's wholly-owned subsidiary (the Israeli Subsidiary). All granted patents related to NurOwn (MSC-NTF cells) manufacturing process and clinical development (families #3 through #6) are fully assigned to and owned by Brainstorm Cell Therapeutics Ltd.
Research and Development
In the year ended December 31, 2022, the company's research and development expenditures were $14,156,000.
Regulations
Any biological products for which the company receives FDA approval are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse effects with the product, reporting of changes in distributed products, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with FDA promotion and advertising requirements.
In the United States, the company's activities are potentially subject to regulation by various federal, state, and local authorities in addition to the FDA, including the Centers for Medicare and Medicaid Services, other divisions of the United States Department of Health and Human Services, the United States Department of Justice and individual United States Attorney offices within the Department of Justice, and state and local governments.
History
The company was founded in 2000. It was incorporated in the state of Washington in 2000. The company was formerly known as Golden Hand Resources Inc. and changed its name to Brainstorm Cell Therapeutics Inc. in 2004.
