VBLT (STRONG BUY)
10/04/16 by BiotechInvest
I have got e-mail with questions about VBLT from one of website users:
"Please your thoughts on Vascular Biogenics (VBLT). I think this small biotech company is a rare gem, but the stock price has fallen and people now say it is a scam. Is the data, presented by them at ASCO16 the real deal?"
After checking company website my answer was:
"I didn't have VBLT on my monitor but now I put it on. I briefly dig their science and honestly I don't see any red flags. VBLT lead anti-cancer drug VB-111 is anti-angiogenic that prevent/inhibit growth of blood vessels within of cancer tissues. They didn't say exactly what the mechanisms of selective inhibition of tumor vascularization by VB-111 but most likely it interferes with specific tumor vascularization VB-111 binds and inhibits“tumor angiogenesis factor” (TAF).
In short words I'm not thinking that VBLT is a scam biotech.
Other pipeline compounds Lecinoxoids is more questionable. VBLT said that they are "structurally and functionally similar to naturally occurring molecules, known as oxidized phospholipids, which possess immune modulating anti-inflammatory proprieties, modified to enhance stability and activity." As far as I know oxidized phospholipids can be toxic and even used as radiomimetics in radiology research.
Any way even VBLT VB-111 is enough for such small biotech to be very valuable. Pps can spike and drop because games of shorts and longs. Current % of funds/institutions is low and for accumulation they need low pps. They accumulate very carefully and can even provoke shorts to increase short positions and decrease pps. They have enough time before main events i.e. Phase III trial results and FDA approval. It's impossible to fight with market so at some point it's better to sell for avoiding losses, then wait for low and enter again before next spike. Summer time is "SELL" time and shorts are in power now."
Later I got one more e-mail from this visitor:
"I sold my VBLT shares today, after I found this post:
Looks like VBLT is a scam. :(
Best regards, M.
When I opened this link I read next comment about VBLT:
"The Feurstein tweets(and others) over the weekend scared me concerning the ovarian cancer data set presented. He talked about the censoring of patients in the ovarian cancer data set left of the median. He and others biotech guys on twitter also raised my eyebrow on the rGBM data set presented.... Scared my weak hands. Nice gain of 10K from my entering point. I might be back if I can counter their logic, but out of the stock for now. If you look at the KM plot on the ovarian data presented at ASCO, you'll notice a lot of censoring of patients left of the 800 day mark. Feurstein's argument is this makes the OS numbers suspect.
More important, as to the rGBM phase II trial. If you look at the initial poster at ASCO from the phase I/11 rGBM trial, the combination arm initially yielded 12 months OS, but then a year later, up to 15 months. There was also a changing of the statistical measurements of the trial, changing of the primary endpoint, and other oddities I've learned over the weekend that freaked me out.
I may be back into the stock when I can learn more that might counter this bearish thesis. David"
Well done to shake weak hands, said I. But what is about VBLT science? It's definitely not scam especially if you open their patents.
What is VB-111?
"VB-111 is a the lead oncology product candidate from our VTS
platform technology, for solid tumor indications, with current clinical
trials in rGBM, thyroid cancer and ovarian cancer.
Our VTS platform technology comprises three components, a viral vector, a promoter and a transgene:
Viral vector—a modified virus that is used as a delivery vehicle to distribute the promoter and the transgene throughout the body.
Promoter—our proprietary, genetically modified promoter, called PPE-1-3X, that specifically targets the endothelial cells of angiogenic blood vessels. When present in these cells, the promoter initiates the expression of the transgene.
Transgene— a genetic sequence designed to yield a specific biologic effect, the expression of which is directed by PPE-1-3X. The particular transgene will vary depending on the therapeutic objectives of the product candidate.
Once the gene therapy has reached the angiogenic blood vessels, the PPE-1-3X promoter activates expression of the transgene to produce a desired protein in the endothelial cells of those vessels. For oncology applications, the transgene selected is designed to destroy angiogenic blood vessels that feed solid tumors. For other potential applications, such as the treatment of ischemia, a different transgene can be selected that is designed to promote the development of angiogenic blood vessels instead of their destruction."
If you are interesting in details you can read patents issued to VBLT here. They also have patent for adenovirus that deliver all 3 components in blood vessels.
After careful reading of patents my conclusion was simple: VBLT is definitely not biotech scam but most likely it's a hidden biotech gem.
Their Phase 3 clinical trial is ongoing:
A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)
Arms Assigned Interventions
Experimental: Arm 1
VB-111 + Bevacizumab
Drug: VB-111 + bevacizumab
VB-111 will be administered intravenously at a dose of 1x10e13 VPs every 2 months
Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks
Active Comparator: Arm 2
Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks
Estimated Enrollment: 252
Study Start Date: August 2015
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Primary Outcome Measures:
Overall survival [ Time Frame: From date of study entry until the date of death from any cause (up to 10 years) ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
Progression Free Survival [ Time Frame: To be assessed from date of randomization until the date of disease progression, assessed up to 10 years. ] [ Designated as safety issue: No ]
Tumor response as measured by RANO Criteria [ Time Frame: To be assessed from date of randomization until the date of disease progression, assessed up to 10 years. ] [ Designated as safety issue: No ]
Bevacizumab, sold under the trade name Avastin, is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels.
Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A). VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer. Bevacizumab was the first clinically available angiogenesis inhibitor in the United States.
Bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for certain metastatic cancers. It received its first approval in 2004, for combination use with standard chemotherapy for metastatic colon cancer. It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain. It had been approved for breast cancer, but that approval was withdrawn when later studies showed no evidence of effectiveness. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. It is listed for its use in treating certain eye diseases.
So, both drugs (used in combination) will hit angiogenesis. And the combination of Avastin + VB-111 may have synergism effect i.e. hit cancer more than single compounds.
So, I have decided to add VBLT to my long-term portfolio at average pps $5. If Phase 3 GLOBE is successful pps can easy spike to $15-20. Acquisition of this biotech with current cap $135M is also possible in 2017.
12/28/2017 by BiotechInvest
Recent update from VBLT as usually didn't have any positive effect on pps:
New Biomarker Data Supports Direct Link between VB-111’s Dual Mechanism of Action and its Clinical Effect on Overall Survival and Progression Free Survival in Recurrent Glioblastoma Multiforme Patients
December 18, 2017
“Our latest analysis has further strengthened our understanding of the highly novel dual mechanism of action of VB-111,” said Dror Harats, MD, CEO of VBL Therapeutics. “We have shown that the survival benefits observed in our rGBM Phase 2 trial are tied to reduced tumor vascularity, which is consistent with what we know about the anti-angiogenic properties of VB-111. In addition, we have demonstrated that VB-111 is associated with fever and immune-mediated responses, including secretion of immune-stimulatory cytokines that correlate with OS as well. The dual mechanism of action is further supported by preclinical data identifying the cell populations and molecular signaling driving this immune anti-tumor response. The data also provide new potential biomarkers that may be useful for clinical analyses. Building upon this, we look forward to additional insights on VB-111 from our pivotal Phase 3 GLOBE trial in rGBM, from which we expect top-line data in the first quarter of 2018.”
The Company’s lead oncology product candidate, VB-111 (ofranergene obadenovec), is a first-in-class biologic agent that uses a dual mechanism to target solid tumors. It utilizes an angiogenesis-specific sensor (VBL's PPE-1-3x proprietary promoter) to specifically target the tumor vasculature
, by induction of cell death in angiogenic endothelial cells in the tumor milieu. Moreover, it is an immune-stimulant that triggers a local anti-tumor immune response, which is accompanied by recruitment of CD8 T-cells and apoptosis of tumor cells.
Well, for investors that understand biology the statements mentioned above mean only one: VB-111 has very high probability to meet primary points in Phase 3 pivotal trial for rGBM under a special protocol assessment (SPA) with the FDA. Of course, analysts like AF will said again that Feuerstein-Ratain Rule is predicting cancer drug failure for small-cap biotechs like VBLT (the F-R Rule is predicting failure for oncology phase III studies undertaken by companies with market caps less than $300 million). VBLT MC now is $203M and in Q1, 2018 will be less $300M. But recently this stupid rule failed for VSTM in Ph3 cancer drug.
So, may be this "rule" has just one simple goal - to scare retail investors and persuade them to sell shares to funds/institutions?
For VSTM it's true:
Increased Positions 40 5,921,225
Decreased Positions 31 1,004,833
Held Positions 9 6,966,380
Total Institutional Shares 80 13,892,438
VBLT in Q3, 2017
Increased Positions 10 90,656
Decreased Positions 13 1,149,742
Held Positions 8 735,213
Total Institutional Shares 31 1,975,611
Funds/institutions were selling. Were they scared by F-R rule? May be. They also believed in AXON AD drug and lost $2B in one day.
Conclusions: VB-111 has >80% probability of success in current Ph3 and pps can easy jump >150-200% after such success.