Company Overview
BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI) is a leading biotechnology company at the forefront of developing innovative autologous adult stem cell therapeutics for the treatment of debilitating neurodegenerative disorders. With a strong focus on ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig's disease, the company has made significant strides in advancing its proprietary NurOwn® technology platform towards potential regulatory approval and commercialization.
Corporate History
BrainStorm Cell Therapeutics Inc. was incorporated in the State of Delaware on November 15, 2006, having previously been incorporated in the State of Washington. In October 2004, the company established its wholly-owned subsidiary, Brainstorm Cell Therapeutics Ltd. (BCT) in Israel, which has since been responsible for conducting all of the company's research and development activities. Over the following years, BCT expanded its presence by forming wholly-owned subsidiaries in the United Kingdom, Israel, and Ireland.
Technology Foundation
The company's foundation is built upon rights to commercialize stem cell technology developed by Ramot of Tel Aviv University Ltd. Leveraging this technology, BrainStorm has focused on developing novel adult stem cell therapies for debilitating neurodegenerative disorders, including ALS, progressive multiple sclerosis (PMS), and Parkinson's disease. The cornerstone of their approach is the proprietary NurOwn process, which involves the propagation of mesenchymal stem cells (MSCs) and their differentiation into neurotrophic factor secreting cells.
Clinical Development
BrainStorm's clinical development journey has been marked by significant milestones. The company has successfully completed two early stage Phase 1/2 trials and a Phase 2 open-label clinical trial of NurOwn in ALS patients. Additionally, a Phase 2 double-blind, placebo-controlled, multicenter clinical trial was conducted, with results demonstrating the tolerability of NurOwn and showing preliminary signs of activity. In a notable achievement, the results of the completed Phase 1/2 and Phase 2 open label trials were published in JAMA Neurology in January 2016, providing valuable scientific validation for the company's work.
NurOwn Technology
The company's lead candidate, NurOwn, is a novel, autologous cell therapy that utilizes the patient's own bone marrow-derived mesenchymal stem cells (MSCs). Through a proprietary manufacturing process, these cells are induced to secrete high levels of neurotrophic factors, which are known to play a crucial role in protecting and repairing damaged neurons. This multi-faceted approach aims to simultaneously target the underlying mechanisms of neurodegenerative diseases, making NurOwn a promising therapeutic option.
The NurOwn manufacturing process involves harvesting the patient's own bone marrow, isolating and expanding the MSCs, and then inducing them to secrete various neurotrophic factors, including GDNF, BDNF, VEGF, and HGF. These factors are critical for the growth, survival, and differentiation of neurons. The differentiated MSC-NTF cells are then transplanted back into the patient, typically via intrathecal administration, with the goal of providing a neuroprotective and immunomodulatory effect to help treat neurodegenerative diseases.
ALS Clinical Development
The company's clinical development efforts in ALS have been particularly noteworthy. BrainStorm has successfully completed a Phase 3 clinical trial for NurOwn in ALS, which, while not meeting the primary endpoint, demonstrated encouraging signals of clinical benefit, particularly in patients with less advanced disease. Building on these insights, the company has now secured a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA) for the design of a Phase 3b registrational trial in ALS.
The SPA agreement represents a significant milestone, as it validates the clinical trial protocol and statistical analysis plan, and provides a clear regulatory pathway for NurOwn's potential approval. BrainStorm is now actively preparing to initiate the Phase 3b trial, which is expected to commence by the end of 2024 or the first quarter of 2025.
On November 10, 2022, BrainStorm announced that it had received a Refusal to File letter from the FDA regarding its Biologics License Application (BLA) for NurOwn in ALS. The FDA indicated that the BLA was not sufficiently complete to enable a substantive review. BrainStorm has since been working with the FDA to address the outstanding issues and resubmit the BLA.
In September 2023, the FDA held an Advisory Committee meeting to discuss BrainStorm's BLA for NurOwn in ALS, and the committee voted that NurOwn did not demonstrate substantial evidence of effectiveness for the treatment of mild to moderate ALS. On October 18, 2023, BrainStorm announced that it would withdraw the BLA.
Despite these setbacks, BrainStorm remains committed to the ALS community and is actively exploring the next steps in support of NurOwn, including publishing clinical data and developing a protocol for an additional clinical study.
Other Clinical Programs
In addition to its work in ALS, BrainStorm has also explored the potential of NurOwn in other neurodegenerative conditions, such as progressive multiple sclerosis (PMS) and Alzheimer's disease (AD). The company's Phase 2 clinical trial in PMS yielded positive top-line data, demonstrating improvements in multiple sclerosis-related functional and cognitive measures.
Financials
BrainStorm's financial position, while challenging at times, has been bolstered by its ability to secure non-dilutive funding sources, including grants from the California Institute for Regenerative Medicine (CIRM) and the National Multiple Sclerosis Society. As of June 30, 2024, the company reported cash, cash equivalents, and restricted cash of approximately $3.65 million, compared to $0.75 million as of June 30, 2023.
For the fiscal year 2023, BrainStorm reported a net loss of $24.28 million, with operating cash flow (OCF) of -$19.32 million and free cash flow (FCF) of -$19.35 million. The company has not generated any revenue to date, as it is still in the clinical development stage.
In the most recent quarter (Q3 2024), BrainStorm reported a net loss of $2.71 million, with OCF and FCF both at -$3.30 million. Research and development expenses for Q2 2024 were approximately $0.9 million, down from $2.8 million in Q2 2023. General and administrative expenses for Q2 2024 were approximately $2 million, down from $2.7 million in Q2 2023. The net loss for Q2 2024 was approximately $2.5 million, compared to a net loss of $5.3 million in Q2 2023.
Liquidity
To further strengthen its financial standing, BrainStorm is actively pursuing additional non-dilutive funding opportunities, including grant applications and strategic partnerships. The company's focus on maintaining a prudent approach to capital allocation has been a key aspect of its long-term strategy.
As of September 30, 2024, BrainStorm had $349,000 in cash, cash equivalents and restricted cash. The company's debt-to-equity ratio stands at -0.1388, with a current ratio and quick ratio both at 0.0514. BrainStorm will require significant additional capital to continue the clinical development and potential commercialization of NurOwn.
The company is actively pursuing non-dilutive funding sources, including a potential grant application that could provide up to $15 million. BrainStorm has financed its operations primarily through public and private equity offerings, as well as non-dilutive grant funding.
Challenges and Opportunities
The road ahead for BrainStorm is not without its challenges. The company faces regulatory hurdles, competition from other emerging therapies, and the inherent risks associated with the development of novel cell-based treatments. However, the company's unwavering commitment to its scientific vision, its strong intellectual property portfolio, and its experienced management team position it well to navigate these obstacles.
Future Outlook
As BrainStorm prepares to initiate the pivotal Phase 3b trial for NurOwn in ALS, the company is poised to potentially deliver a significant breakthrough for patients suffering from this devastating disease. With the SPA agreement in place and a refined patient population, the upcoming trial offers renewed hope for the ALS community and the potential to unlock long-awaited therapeutic options.
BrainStorm has reached alignment with the FDA on the Chemistry, Manufacturing, and Controls (CMC) aspects of the Phase 3b trial. The company has selected a leading Contract Research Organization (CRO) and is building a network of over 12 leading clinical centers across diverse geographic regions to conduct the trial. The manufacturing processes for NurOwn are well-advanced, and the company believes they are on track to meet production timelines for the trial.
Conclusion
BrainStorm's journey in the field of neurodegenerative diseases has been marked by scientific advancements, clinical progress, and a steadfast commitment to improving the lives of patients. As the company continues to execute on its strategic priorities, investors and the broader healthcare community will eagerly follow the unfolding story of BrainStorm Cell Therapeutics and its pursuit of game-changing therapies. The upcoming Phase 3b trial for NurOwn in ALS represents a critical juncture for the company, with the potential to reshape the landscape of ALS treatment and pave the way for further applications of its innovative cell therapy platform.