Pan American Health Organization PAHO via Flickr
In 2002, a neuroscientist and surgeon at the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment at the Swedish Neuroscience Institute published a paper in the Journal of Cancer research. The paper (available here), detailed a potential link between a highly prevalent virus called cytomegalovirus (CMV) and an aggressive, and common, form of brain cancer called glioblastoma multiforme (GBM). For at least a decade before this publication, the link had been hypothesized in various centers across the globe, but no institute had set out to formally demonstrate that it exists.
As such, the neuroscientist in question, Dr. Charles Cobbs, and his research team, expected a wave of interest in the field based on his publication. As it turned out, this wave of interest didn’t materialize; at least not immediately. For two years post-publication, it seemed as though the journal article had gone unnoticed. Then, in 2004, Cobbs received a phone call from renowned oncology research institution Duke University. The University had built on the evidence presented by Cobbs and his team, in an attempt to identify a real world application of the suggestion that the CMV virus is somehow linked to GBM development.
Subsequent research conducted as a collaboration between Cobbs and Duke hypothesized, and subsequently concluded, that GBM cells are susceptible to infection by CMV virus, and more than 90% of said cells express antigens specific to the CMV virus.
The science is still debated pretty hotly, but in the five or so years subsequent to publication of the Duke research, more and more of the medical community are shifting in line with the research’s conclusion.
A large portion of the preclinical and development stage assets we see in the biotechnology space derive from exactly this sort of conceptual research. What starts off as a small, inconclusive hypothesis is built on by individuals, and then teams of researchers, and then universities, before being picked up by biotechnology companies and carried into clinical development.
The GBM CMV link is at this latter stage right now.
A company called VBI Vaccines, Inc. – Ordinary Shares (NASDAQ:VBIV) is attempting to use the research to underpin the development of a vaccine based therapy, designed as an immunotherapy asset targeting GBM.
The drug is called VBI 1901.
Before we get into how it works, and for those not familiar with this company, it is worth kicking things off with a brief introduction. VBI is a vaccine therapy-focused biotechnology company headquartered in Cambridge, Massachusetts. The company has a hepatitis B vaccine already on the market in a range of countries globally, and which is currently working towards approval in the US. The vaccine is built on a platform that is proprietary to VBI, and is able to produce what are now referred to as third-generation vaccines. We won’t go into too much detail as to what these third-generation vaccines are right now, however, suffice to say, they improve upon the immunogenicity and safety of the first and second generation vaccines through the mimicry of the viruses they are designed to target. Put simply, the closer a vaccine resembles a virus, the higher its effectiveness in immunizing a person against said virus. VBI’S proprietary technology allows the company to create vaccines that are more similar to target viruses than ever before, and therein lies the company’s advantage.
In the case of GBM, however, and VBI 1901, it is not immunogenicity that is the focus. Instead, the company is trying to elicit an immune response that targets GBM cancer cells. Those familiar with immuno-oncology will likely already be familiar with this sort of process. Basically, an immunotherapy drug seeks to activate a person’s immune system against a focus disease cell. Without the drug, the cells are often overlooked by the immune system, and are able to proliferate uninhibited. By eliciting an immune response, however, an immuno-oncology drug can teach the immune system to recognize the disease cells, and activate against them. T cells target and kill the cells in question, and then white blood cells (typically things like macrophages) swoop in and clean up the mess.
Wellcome Images via Flickr
Now, at the core of this process, is the ability to teach the immune system to recognize the unwanted cells, and in this instance, the cancerous GBM cells. Also important is the ability to help the immune system differentiate between cancerous cells and healthy cells. This is where CMV comes into play. Because GBM cells are susceptible to CMV infection, they express antigens unique to the CMV virus. An antigen is a molecule expressed on the membrane of a cell that is recognizable by antibodies in the immune system. When an antibody recognizes an antigen, it links to it and – by way of this link – signals to T cells that the cell in question is foreign and needs to be removed.
VBI-1901 recognizes and directs an immune response against gB and pp65, two CMV antigens that are highly immunogenic targets during natural infection. Both antigens are expressed to a high degree on GBM cells, but – and this is important – are not expressed (at least not usually) on healthy cells.
So That Is the Scientific Concept and Its Origin… What About Development?
This is why we are highlighting this company right now.
In October of last year, VBI sat down with the FDA as part of a pre-IND meeting to discuss a development pathway for the VBI-1901 asset.
According to the press release published just after the meeting took place, The FDA addressed VBI’s questions related to preclinical data and planned clinical trial design and provided greater clarity on the requirements needed to file an IND to initiate a Phase 1/2a clinical trial in patients with GBM.
As a quick note for those new to the space, an IND is a filing required by the FDA for any new clinical compound. Essentially, it is a document saying “this is the drug we are looking to develop, this is what it is (etc.) and this is how we plan to conduct the early stages of our clinical trials.” Once submitted, the agency will approve or deny the application and an approval opens the door to clinical development.
With a pre-IND meeting, the chances of approval for an IND at first submission are dramatically improved. Why? Because the company knows exactly what it needs to do and say before submitting, so it is essentially a box ticking exercise.
VBI expects to submit its IND for VBI-1901 during the first half of 2017, opening up the potential for phase 1/2a trial initiation before the end of the year.
Glioblastoma is among the most common and aggressive malignant primary brain tumors in humans. In the US alone, 12,000 new cases are diagnosed each year. Current standard of care is surgical resection, and even with successful treatment, survival is measured in months, not years. If VBI can carry this drug through to commercialization, therefore, there is a huge potential market, and one that could catapult VBI into the upper echelons of immunotherapy biotechnology companies.
Further, this isn’t even the company’s lead asset. VBI is developing a vaccine targeting the CMV virus (a program from which the GBM asset was born) and expects to put out interim data from this a phase 1 study in this indication over the coming couple of months. We should also see some will take us to the regulator he progress of SciBVac, the hepatitis B vaccination mentioned above, in the US and Europe next quarter. Both developments serve as near term catalyst, and should inject some upside momentum into the stock as they hit press (assuming they read positively).
Management and institutional backing is also strong. Among the company’s most well-known investors are Dr. Philip Frost, billionaire healthcare on thinner and subject update Forbes Magazine focus piece on biotechnology investment; and Dr. Steven Gillis, Managing director at Arch Venture Partners, a biotech VC with $1.9B under management, who serves as chairman of the board at VBI.
The GBM asset is only one of a host of potential applications of this company’s technology, and each of the assets that comprise its pipeline have the potential to generate revenues that greatly exceed VBI’s current market capitalization. It’s a young biotechnology play, so it’s not without its risks (capital raise, trial data misses, etc.), but as a diversified exposure to vaccines and immunotherapy, it could be a potential winner.
Author has no position in any company mentioned in the article above, but may or may not take a position at a later date.