This level of disease stabilization has not been observed to this date in approved or investigational ALS therapies.
- Mr. Chaim Lebovits, CEO, Brainstorm Cell Therapeutics
In May of this year, I published an article on Brainstorm Cell Therapeutics (BCLI). This small company is developing a mesenchymal stem cell product called NurOwn, which is in late phase 3 trials targeting amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. My article was bearish, deploring not only the company's cash position but also phase 2 trial data. The article can be read here.
That article received a lot of critical comments from the ALS community. That made me realize that a fair overview of the issues could be best addressed by going through the comments, as well as my own coverage, and by asking BCLI management, specifically its CEO, Chaim Lebovits, to clarify some of these issues. So, that's what I did. I emailed a set of 11 questions to Mr. Lebovits, and he was kind enough to respond to them in great detail. The entire interview, sans any edits, is available to Total Pharma Tracker members.
Mr. Lebovits has been with BCLI for well over 12 years, joining in 2007 as president and also becoming the CEO in 2015. He has helped develop NurOwn through its preclinical stage to its current stage and is, therefore, just the right person to talk to if we want to understand NurOwn and BCLI.
I began by asking him to locate NurOwn in the ALS therapy space and where it stands with respect to competitors. What's its mechanism of action, and how does that MOA distinguish it from the competition?
Mr. Lebovits said that there are "currently 4 products active in phase 3 ALS clinical trials (Brainstorm (NurOwn, autologous MSC-NTF cells secreting neurotrophic factors), Orion (levosimendan, muscle troponin calcium sensitizer), Orphazyme (arimochlomol, heat shock protein enhancer), and Biogen (SOD1, antisense oligonucleotide)." Top-line data from these ALS phase 3 trials is expected in 2020 (Q4 2020 for Brainstorm) and Orion, 2021 (Orphazyme), and 2022 (Biogen). He discussed a number of earlier-stage compounds as well as various stem cell therapies. He said that what distinguishes NurOwn among ALS therapies is that it "confers both neuroprotection and immunomodulation by delivering neuronal survival factors and immune regulatory molecules, including microRNA directly to the CNS compartment at or near the site of disease, and therefore directly addresses two important ALS disease mechanisms."
Among stem cell therapies, Mr. Lebovits said that NurOwn distinguishes itself by being autologous and because it can produce high levels of neurotrophic factors. Moreover, unlike most stem cell competitors, it's delivered directly into the spinal fluid through bimonthly lumbar punctures, unlike others that need an invasive surgical procedure "that carries considerable morbidity."
This feature it shares with a competing product from Corestem. However, it's differentiated from Corestem because "NurOwn is more convenient than the Corestem product as a single bone marrow cell harvest due to validated cryopreservation, whereas the Corestem product requires repeat bone-marrow aspiration for each treatment."
My next question was a technical question about pharmacoresistance. I wanted to know how NurOwn is managing to cross the blood-spinal cord barrier despite the strong pharmacoresistance (body's resistance to drugs) seen in ALS, specifically for disease-modifying neurotrophic factors. What was it about NurOwn's delivery mechanism that the company thinks is overcoming this natural resistance. So I asked: "Talking about MOA, pharmacoresistance is a disease driving mechanism in ALS. Can you discuss NurOwn's delivery mechanism vis-a-vis the inability of neurotrophic factors to effectively cross the blood-brain barrier, or, specifically, the blood-spinal cord barrier (BSCB)? Please correlate that discussion regarding the observed increase in CSF NTFs post-treatment as seen in the phase 2 trial."
Mr. Lebovits explained this with great clarity - for his entire response, take a look at the complete interview. Broadly, what he said was that NurOwn, being delivered through lumbar puncture directly into the spinal fluid, has an advantage. Moreover, the cells secrete neuronal survival factors as well as molecules that regulate the immune system, so that they are able to survive and overcome the pharmacoresistance. Systemically administered NTFs are unable to do that.
As he said, "In the phase 2 trial, CSF biomarkers obtained just prior to treatment and two weeks afterward demonstrated that MSC-NTF cell-secreted neurotrophic factors were significantly increased post-treatment and correlated with the reduction in inflammatory biomarkers, consistent with the proposed mechanism of action."
My third and fourth questions related to aspects of the phase 2 study. One, comparison of safety and efficacy data with competitors, and two, the relevance of the reported caspase-3 reduction of 60% in responders versus 30% in non-responders.
Mr. Lebovits said that although the phase 2 study was not powered for efficacy, it exhibited a "level of disease stabilization (that) has not been observed to this date in approved or investigational ALS therapies." About the ongoing phase 3 study, he said the following:
Those who read my original article will recall I was particularly puzzled by the increased occurrence of serious adverse events in active-treatment groups than in placebo groups. 8/36 or 22.2% patients in the treatment arm had an SAE compared to only one out of 12 placebo patients, or 8.3%. Most SAEs were related to the progression of the underlying ALS, most commonly dysphagia. No SAEs were related to study treatment. So I asked Mr. Lebovits how this data could be interpreted in the most positive way.
According to him, this decline was not an effect of treatment itself and simply indicated the need for repeat dosing in this patient group. His exact response was as follows:
The MSC-NTF treated group had a slightly more rapid rate of decline compared to the placebo group in the three-month run-in period and most ALS disease progression in the treated group was seen toward the end of the clinical trial, long after a single transplantation. In fact, the bulbar subscale, that includes assessment of swallowing, was the subscale most improved after MSC-NTF treatment in rapid progressors, suggesting that the late decline in motor function was not an adverse effect of treatment per se. Hence the need for repeated dosing.
Last week, the DSMB recommended continuation of the phase 3 trial without any modification. This was major good news, so we asked him about this. Mr. Lebovits said that this was a second interim safety review, and there were no significant safety concerns. Therefore, the DSMB recommended no modification in protocol and no other interim analysis is planned. Phase 3 data will be available by mid-2020 according to this interviewer's reading of the press release.
Now we moved on to another critical aspect of our analysis - funds, or rather, the lack of it. Since this is an important issue, here's the exact exchange we had.
Dr. Ashok Dutta: How does the company plan to fund its operations through the next couple years until the lead development candidate is approved and commercialized? Given the weak financial position, does Brainstorm see the possibility for ATM operations, or thinks about selling rights in regions like China, Japan or Europe to increase the financial condition?
CEO Chaim Lebovits: As you are aware we do receive proceeds from the hospital exemption pathway and also receive grant funding from CIRM and IIA. These avenues have allowed to fund and continue with our trials over the years with non-dilutive financing. From a business standpoint as our ALS phase 3 trial is now fully enrolled, the management team continues to hold high level conversation with some of the leading global pharmaceutical and biotechnology companies. We are actively engaged in strategic partnering and collaboration discussions and although we cannot disclose the details of our conversations due to NDAs we signed with them... we are exploring several opportunities with key interested parties to advance the opportunities for NurOwn development and commercialization. As you have rightly pointed out, we have a $20mm ATM facility in place with Raymond James. We may activate the ATM as required and raise up to $20mm by selling our stock "at the market" only if the prices are attractive to us. So far as of end of Q3'19, we have not activated the ATM. If the need arises and the prices are attractive to us, we may employ this tool to raise capital.
This is reassuring that the company intends to focus on non-dilutive financing. The ATM facility, coupled with the grants, should ideally see them through the approval phase. We still wonder how they will manage marketing and sales. Perhaps those commercialization NDAs they have signed will help.
Next, we discussed market potential and a question about a recent patent grant. The CEO's detailed responses can be found in the complete interview material.
The strong involvement of the ALS community impressed us previously, so we now asked the CEO about the recent roundtable convention they had with ALS advocacy groups. Since this will be important for the ALS community as a whole, here's Mr. Lebovits' entire response on the question:
Finally, we asked him what we ask everyone: Give us three simple and straightforward reasons why investors would be interested. Here's what he said:
Thanks to the ALS community for inspiring us to conduct this interview, and to Mr. Chaim Lebovits, CEO of Brainstorm Cell Therapeutics, for answering our questions.
Thanks for reading. At the Total Pharma Tracker, we interview management of important small biotech doing disruptive work in healthcare. Our members are given exclusive access to these interviews, which helps them with additional primary resource in doing DD on their investments. Sometimes, extracts from these interviews may be published for everyone; but TPT members always get the exclusive view.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
Additional disclosure: General Disclaimer - This is to confirm that Avisol Capital Partners has neither requested, nor been offered, any monetary compensation for conducting this interview, by any party other than Seeking Alpha.
Also to be noted, this was an emailed questionnaire, and certain editorial material is present in this version, which may or may not reflect BCLI or its CEO's position on the issues discussed.
Read the original here:
Interview With Chaim Lebovits, CEO Of Brainstorm Cell Therapeutics - Seeking Alpha
- Aspen Neuroscience gets funding to pursue personalized cell therapy for Parkinsons disease - The San Diego Union-Tribune - December 14th, 2019
- Acute Leukemia: 5 Things to Know - Medscape - December 14th, 2019
- Global T-Cell Therapy (CAR T-Cell, Tumor Infiltrating Lymphocytes) Market Size, Share & Trends Analysis Report 2019-2026 - ResearchAndMarkets.com... - December 14th, 2019
- CAMPUS: EGG DONATION - Artificial sperm cells to remove the genetic worries of sperm donation - ESHRE - December 14th, 2019
- Stem Cell Therapy Market Forecasted To Surpass The Value Of US$ XX Mn/Bn By 2045 2017 - 2025 - Markets Gazette 24 - December 14th, 2019
- Aspen Neuro Bags $6.5M to Test Parkinson's Disease Stem Cell Therapy - Xconomy - December 13th, 2019
- LentiGlobin Gene Therapy Continues to Show Promising Results in SCD, Updated Trial Data Shows - Sickle Cell Anemia News - December 13th, 2019
- CHMP Issues Positive Opinion Recommending DARZALEX (Daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone in Frontline Multiple... - December 13th, 2019
- Treatment Characteristics and Outcomes for Patients With Rare Forms of T-Cell Lymphoma - Hematology Advisor - December 13th, 2019
- Researchers ID Molecule that Appears to Halt and Reverse Scarring in Fibrotic Diseases - BioSpace - December 13th, 2019
- Canine Stem Cell Therapy Market with Future Prospects, Key Player SWOT Analysis and Forecast To 2024 - Tech Estate Today - December 13th, 2019
- StemGenex - Stem Cell Therapy, Stem Cell Treatments, Stem ... - December 11th, 2019
- Cutting Edge Exosome Regenerative Therapy Comes to Yelm's AM Medical - ThurstonTalk - December 11th, 2019
- Sickle Cell Disease: Ex Vivo Cell Therapy Shines in Early Study - MedPage Today - December 11th, 2019
- Five recent drug target discoveries for pancreatic cancer - Drug Target Review - December 11th, 2019
- Immunotherapy drug improves outcomes for some children with relapsed leukemia - National Institutes of Health - December 11th, 2019
- 20(R)-Ginsenoside Rg3 Influences Cancer Stem Cell Properties and the E | OTT - Dove Medical Press - December 11th, 2019
- Patients closer to receiving regenerated tissue, scientists say - The Irish News - December 11th, 2019
- The Knesset dissolves and the public suffers - Ynetnews - December 11th, 2019
- Global T-Cell Therapy Market: Trends, Opportunities and Forecasts (2019-2026) - Therapy for Solid Tumors Expected to Emerge as a Lucrative Source of... - December 11th, 2019
- Layoffs at Fla.-based stem cell clinic accused of aggressively marketing patients - ABC Action News - December 11th, 2019
- Lineage Cell Therapeutics and AgeX Therapeutics Announce Issuance of US Patent for Method of Generating Induced Pluripotent Stem Cells - BioSpace - December 11th, 2019
- New Mechanism of Bone Maintenance and Repair Discovered - Technology Networks - December 11th, 2019
- BMS' oral maintenance therapy boosts survival in AML patients - PMLiVE - December 11th, 2019
- Autoimmune Technologies Announces New Subsidiary to Develop Novel Antibody and Allogeneic Somatic Stem Cell Therapeutics For the Treatment of Invasive... - December 10th, 2019
- Microbial Dynamics in Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation - Oncology Nurse Advisor - December 10th, 2019
- CStone's anti-PD-L1 antibody demonstrates promising antitumor activity with a complete response rate of 33.3% and a good safety profile in patients... - December 10th, 2019
- Celularity Presents Pre-Clinical and Clinical Data from its Allogeneic, Placental-Derived, Off-the-Shelf Cell Therapy Platform at the 2019 ASH Annual... - December 10th, 2019
- Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug... - December 10th, 2019
- Novartis sets 2020 target for commercial readiness of cell therapy CMO - BioPharma-Reporter.com - December 10th, 2019
- Stadius Biopharma to Present Data on Fully Human Antibodies for the Treatment of Candida Infections - P&T Community - December 10th, 2019
- Seattle Genetics and Takeda Announce Additional Analyses of ADCETRIS (Brentuximab Vedotin) ECHELON-1 and ECHELON-2 Phase 3 Clinical Trials at the 2019... - December 10th, 2019
- ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment - OncoZine - December 10th, 2019
- IFN-: The T cell's license to kill stem cells in the inflamed intestine - Science - December 8th, 2019
- Movies opening in L.A. this week: 'Bombshell,' 'Jumanji: The Next Level' and more - Los Angeles Times - December 8th, 2019
- Updated Clinical Data from Phase 2 SPiReL Study Evaluating DPX-Survivac as a Combination Therapy in r/r DLBCL Presented at 61st American Society of... - December 8th, 2019
- Stem Cell Alopecia Treatment Market 2019 Business Growth, Size and Comprehensive Research Study Forecast to 2026 - Montana Ledger - December 8th, 2019
- Jasper Therapeutics launches out of Stanford with new approach to stem cell treatment - Endpoints News - December 7th, 2019
- MaaT Pharma Announces the Presentation of Positive Data with Its Lead Microbiome Biotherapeutic in Intestinal-Predominant Acute... - December 7th, 2019
- Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - GlobeNewswire - December 7th, 2019
- Sickle Cell Anemia Patient Becomes First Person in the US to Have Her Genes Edited With CRISPR - Interesting Engineering - December 7th, 2019
- Teen diagnosed with cancer again just months after being told he beat disease - Mirror Online - December 7th, 2019
- Living with cancer: 'Exercising during my chemotherapy treatment worked wonders' - inews - December 7th, 2019
- Takeda to Present Results from the Phase 3 TOURMALINE-AL1 Trial of NINLARO in Patients with Amyloidosis - Business Wire - December 7th, 2019
- Stem cells may trigger immune repair to mend hearts - BioNews - December 5th, 2019
- Omeros Reports Positive Data Across Primary and Secondary Endpoints in Pivotal Trial of Hematopoietic Stem Cell Transplant-Associated Thrombotic... - December 5th, 2019
- Hunter Syndrome Treatment Market Size, Share & Trend Analysis By Treatment, By Region And Segment Forecasts, 2019 - 2026 - P&T Community - December 5th, 2019
- Platelet Rich Plasma and Stem Cell Alopecia Treatment Market is on Course to Expand at a CAGR of XX% Over the Forecast Period 2018 - 2026 - Weekly Spy - December 5th, 2019
- miR-194 Inhibits the Proliferation of SW620 Colon Cancer Stem Cells Th | CMAR - Dove Medical Press - December 5th, 2019
- Stem Cell Therapy Market Growth opportunities, Trends, Industry Analysis, and Forecast to 2020 - Kentucky Reports - December 5th, 2019
- As per new Study on Stem Cell Therapy Market 2019 Future Strategy, Analysis and Prediction by Leading Manufacturers, its Application and Types... - December 5th, 2019
- Stem Cell Therapy Market Size, Share, Trends, and Opportunity Analysis by 2017 - 2025 - The Market Expedition - December 5th, 2019
- Newly approved sickle cell drug ushers in an era of therapeutic breakthroughs - Worcester Telegram - December 5th, 2019
- A new stem cell therapy promises to heal injured heart - TheHealthSite - December 5th, 2019
- Harnessing Gamma T Cells To Bring Effective Therapies to Patients - Technology Networks - November 30th, 2019
- Phase 2 Trial Data on ALS NurOwn Therapy, Supporting Safety And Early Efficacy, Published - ALS News Today - November 30th, 2019
- Proof-of-Concept Study of CAR-NK Cell Therapy with Engineered Persistence Shows Potential - Cancer Network - November 29th, 2019
- Mum shares heartbreaking photo of toddler sobbing through gruelling cancer treatment - The Sun - November 29th, 2019
- Mesenchymal Stem Cells Market Key Trends, Key Players, Challenges And Standardization, Analysis Of Key Players, And Forecast To 2026 - WindStreetz - November 29th, 2019
- Bone Therapeutics SA: Information on the total number of voting rights and shares - GlobeNewswire - November 29th, 2019
- Induction Therapy and Hematopoietic Stem Cell Transplantation for Mixed-Phenotype Acute Leukemia - Cancer Therapy Advisor - November 28th, 2019
- Why Stem Cell Therapy Might Be Your Answer To Chronic Pain - Patch.com - November 28th, 2019
- North-east toddler overcomes cancer after pioneering stem cell treatment - Press and Journal - November 28th, 2019
- Revolutionary stem cell banking and therapy from Celltex gives patients hope - KHOU.com - November 28th, 2019
- Kyoto University seeks approval to use stem cells in treatment for damaged knees - The Japan Times - November 28th, 2019
- Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy - Science Advances - November 28th, 2019
- Sickle Cell Disease: Current Treatment and Emerging Therapies - AJMC.com Managed Markets Network - November 28th, 2019
- Vertex plans major Boston expansion to support gene, cell therapy ambitions - FiercePharma - November 28th, 2019
- Discovery of 'Tendon Stem Cells' Could Revolutionize How We Recover From Injuries - Good News Network - November 28th, 2019
- You can take my Dads tweets over my dead body - TechCrunch - November 28th, 2019
- From Tiger Woods to Brooks Koepka, the 9 things we learned this fall on PGA Tour - Golf Channel - November 28th, 2019
- Platelet Rich Plasma and Stem Cell Alopecia Treatment Market Future Growth, Industry Verticals, and Research Forecast upto 2026 - The Denton Chronicle - November 28th, 2019
- Stem Cell Therapy Market Gain Impetus due to the Growing Demand over 2025 - Guru Online News - November 28th, 2019
- Stem Cell Therapy Market Size, by Therapeutic Application (Musculoskeletal Disorders, Wounds and Injuries), by Cell Source (Adipose Tissue-derived... - November 28th, 2019
- Global Musculoskeletal Disorder Stem Cell Therapy Market 2019 by Manufacturers, Countries, Type and Application, Forecast to 2025 - Avon Lake Ledger - November 28th, 2019
- Translink in Armagh holding stem cell registration event in memory of Gavin McNaney - Armagh i - November 28th, 2019
- Induction Therapy and Hematopoietic Stem Cell Transplantation for Mixed-Phenotype Acute Leukemia - Hematology Advisor - November 25th, 2019
- Tendon stem cell discovery could lead to improvements in injury recovery - Drug Target Review - November 25th, 2019
- 2 Small-Cap Biotechs That Soared Last Week - Motley Fool - November 25th, 2019
- Cell Culture Market Size to Exceed US $42 Billion by 2026 - Post Register - November 25th, 2019