Sign up to SCR Digest, our FREE weekly newsletter, and receive our Notes emailed directly to you.
Email Address *
First Name
Mailing Lists *




















































































































VBI: Multiple Platforms Yield a Portfolio of Vaccines

11/13/2017


NASDAQ:VBIV

VBI Vaccines, Inc. (NASDAQ:VBIV) is a Cambridge, Massachusetts-based biopharmaceutical company developing a portfolio of vaccines including solutions for hepatitis B, cytomegalovirus (CMV) and glioblastoma multiforme (GBM).  VBI has three main drivers in its portfolio of products which include further advancement of the Sci-B-Vac Phase III trial in the US, read out for Phase I trial for CMV and launch of the GBM Phase I/IIa clinical study.  The company also has several other candidates in early stage development, including collaborations with Sanofi and GlaxoSmithKline which employ the company’s lipid particle vaccine (LPV) program.  LPV is expected to improve the distribution of vaccines in environments with volatile temperatures.  This is particularly useful in developing countries where refrigeration is unavailable or unreliable.


VBI has eight programs in its pipeline with Sci-B-Vac the most advanced and ready to start Phase III trials before the end of the year.  Cytomegalovirus is not far behind and is expected to provide a read out of its Phase I trial in the first half of 2018.  The other programs are in preclinical stages and range from a Zika vaccine to undisclosed projects with some of the most dominant global pharmaceutical companies.  Below we provide the company’s graphic on each development project and its stage.



Vaccines

Vaccines are a biological approach to generating an acquired immunity to a disease.  The vaccine itself has the characteristics of the target pathogen and the body responds to the vaccine by creating antibodies, destroying the invader and remembering its signature for the next encounter.  Vaccines have a long history, with some evidence supporting the use of the approach in India and China in the 10th century.  Modern vaccines began to emerge in the 19th and early 20th century with polio, tetanus, typhoid and other vaccines becoming available.  Live vaccines were first used with cowpox and smallpox for example, and later the approach was refined to provide live-attenuated viruses.  As vaccines evolved, subunit approaches were used which employed a fragment of a pathogen, including only the surface proteins that appear on the virus.  More recently, virus-like particles (VLPs) have been used.  VLPs are manufactured in the lab with first-generation examples such as Gardasil, Cervarix and Engerix-B.  The platform has progressed in the last several years to advance a VLP that very closely imitates a virus which is easily recognized by the immune system. 

eVLP Platform

The basis of the company’s solely owned development portfolio is its enveloped virus-like particle (eVLP) platform which patterns the structure of the vaccine after the target virus.  eVLPs do not contain the viral genome, so they pose no risk of infecting the patient but they do present the viral antigens on their surface.  In response to the antigens, T-lymphocytes and antibodies recognize and multiply, retaining a memory of the antigen signature for the future.


The eVLP technology is the basis for five development products at VBI, ranging from the preclinical GBM candidate to the Phase I CMV program.  This technology was acquired through the purchase of VBI Cda and ePixis SA.  It is the basis for the synthetic manufacture of an enveloped virus-like particle, which is a similar structure to enveloped viruses that are surrounded by a lipid bilayer membrane.  The VLP lacks the viral genome, providing a safer and more potent vaccine product.  Virus like particles (VLPs) resemble viruses, but are non-infectious as they do not include viral RNA or DNA.  On the surface of the bilayer, antigens are present.  These can be recognized by T- and B-cells and activate the body’s immune response as the structure of the VLP resembles the expression of antigenic proteins as they naturally occur.  The benefit of having a particle that closely mimics the structure of a virus is that it significantly improves the immunogenicity of the vaccine compared to previous generations of VLP structures. 

The key advantages of this approach is the availability of a highly immunogenic vaccines that are customizable, safe and commercially viable.  Manufacturing of eVLPs is an efficient process that can produce high yields with exceptional purity.  In some academic settings, optimized manufacturing processes have reduced the cost of producing eVLP vaccines to very low levels.  

Sci-B-Vac

Sci-B-Vac is a next generation hepatitis B virus (HBV) vaccine that mimics three viral antigens rather than the single antigen in second generation vaccines.  Sci-B-Vac includes the S-protein, Pre-S1 and Pre-S2 and contains an aluminum-based immunologic adjuvant, which stimulates the immune system.  The benefit of this advanced vaccine is that it can block both the binding and the fusion of HBV onto liver cells.  The vaccine is approved in 15 countries and currently being marketed in Israel and Hong Kong.  Over 300,000 patients have received the product and 22 clinical trials have been completed, providing a large sample size in support of the safety profile for the current effort to launch a Phase III trial in the US.


Hepatitis B is a widespread virus throughout the world, especially in Asia.  It is estimated that 2 billion people have been infected with HBV and that 240 to 350 million persons are chronically infected and contagious.  From 600 to 900 thousand are dying directly and indirectly from the disease every year according to data from the WHO, the CDC and GBI Research.  While there has been a vaccine program in place for many years, it has not been consistently applied.  While the current standard of care, GSK’s Engerix-B is widely used, it is not highly effective in older or high risk patients.  According to data provided by the company, current seroconversion rates for Engerix-B range from 99% for children and drop to approximately 50% for those over age 59.  Additionally, those with liver disease, renal failure, HIV infection, and other immunosuppression only experience a 50% to 70% seroconversion rate following the HBV vaccination.


With the declining rate of vaccine effectiveness in successively older patients for current vaccines, and the relatively low level of effectiveness in at-risk populations, there is an unmet medical need for a next-generation vaccine that can address non-responders.  Sci-B-Vac has demonstrated safety and efficacy in over 100,000 patients, including infants and can augment the standard of care.  

VBI held discussions with the FDA, EMA and Health Canada during the first part of 2017 to obtain input regarding clinical trial design.  In late August the company announced successful interactions with all three regulatory agencies and that the FDA had accepted its new drug application for a Phase III clinical trial.  Based on the input from the FDA, Health Canada and the EMA, VBI has designed two concurrent trials that will enroll 4,800 subjects.  The first study called PROTECT addresses safety and immunogenicity and the second called CONSTANT examines lot-to-lot consistency.  About 40 clinical trial sites are expected to be used for both trials in the US, Europe and Canada.  

The PROTECT trial is a double blind randomized controlled trial to compare the immunogenicity and safety of a 3-dose regimen of Sci-B-Vac to a 3-dose regimen of Engerix-B (GlaxoSmithKline’s vaccine) in adults.  The patients will be stratified by age group, and 10 µg of SBV or 20 µg of Engerix-B will be administered at month 0, 1 and 6.  Primary endpoints will be non-inferiority of SBV 4 weeks after 3rd vaccination for all enrollees and superiority of Sci-B-Vac 4 weeks after 3rd vaccination in adults 45 or older.  Secondary endpoints will measure non-inferiority of Sci-B-Vac after two vaccinations (measured at four weeks) compared to Engerix-B at four weeks after the 3rd vaccination.  Safety and reactogenicity of both vaccines will also be examined.

The CONSTANT study is a double blind randomized controlled trial to assess the lot-to-lot consistency of Sci-B-Vac in adults.  3,200 subjects will be enrolled with ages ranging from 18 – 45.  The goal of the study is to examine consistency across production lots.  Three of the arms will consist of 10 µg of Sci-B-Vac and one will consist of 20 µg of Engerix-B, as a control.  The primary endpoint is a measure of manufacturing equivalence between the lots measured four weeks after the third vaccination.  Secondary endpoints will examine immunogenicity and safety compared to Engerix-B.  

VBI is currently working with one of the largest, but unidentified, contract research organizations in the world to begin the Phase III work.  Cost estimates for the trial are from $8 to $10 thousand per enrollee in the United States and somewhat less than this amount in Canada and Europe.  With 4,800 subjects, our best estimate is for all-in costs of just below $40 million to conduct the study.  

Cytomegalovirus

The cytomegalovirus (CMV) is a common virus which has no or a limited impact on individuals with normal, developed immune systems.  However, in babies and those with weak immunity, serious symptoms can emerge such as damage to eyes, lungs, liver, esophagus, stomach and intestines.  The virus can also harm a fetus, causing deafness and mental retardation.  Currently, there is no approved vaccine for CMV despite the incidence of over 5,000 related medical conditions to CMV per annum.  

VBI is now developing a CMV vaccine called VBI-1501A which uses the eVLP technology to construct a particle that presents the glycoprotein B (gB) antigen on its surface to the immune system.  VBI-1501A improves on prior attempts to construct a CMV vaccine by increasing potency, improving delivery to multiple cell types and expanding the duration of protection.  A previous vaccine provided 50% immunity, however, VBI was able to improve on this by presenting the antigen on the eVLP and modifying the gB antigen thereby substantially improving its potency.  To increase the duration of immunity an alum stabilizer was added to the compound to increase the stability and durability of the immune response.

The vaccine is currently in a Phase I trial which began in mid-2016 and all patients received their third and final immunization by the beginning of May 2017.  The primary endpoint for the trial is the occurrence of adverse events while the secondary endpoints are the volume of anti-CMV neutralizing antibodies and binding titers and avidity measurement directed against gB six months after the third dose.  The trial will have five arms, with the CMV vaccine administered at 0.5 µg, 1.0 µg, 2.0 µg all with alum, and 1.0 µg without alum as well as a placebo arm.  Final readout is expected in the first half of 2018.  

Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is an aggressive brain cancer which expresses specific antigens that may respond to treatment such as vaccination with viral epitopes, such as the ones that can be expressed on the surface of eVLPs.  Several studies have detected CMV antigens in GMB tumors and CMV-specific T-cells have destroyed primary GBM cells a clinical study.   The study employed CMV pp65 RNA-transfected dendritic cells, identifying pp65 as a beneficial therapeutic target.  VBI is augmenting its VBI-1501A candidate with an internal pp65 protein to stimulate a Th1 (T-helper cell) response which aids in the proliferation of CD8+ and CD4+ T-cells.


This program has conducted and completed extensive pre-clinical work, held its pre-IND meeting with the FDA and both submitted and had its IND accepted by the FDA.  The company expects to begin enrollment in the Phase I/IIa trial in 4Q:17.  Biomarker analysis and initial efficacy data are expected to be presented in the second half of 2018.  

Liquid Particle Vaccine (LPV) Thermostability Platform

Most vaccines require refrigeration and maintenance within a narrow temperature range from their initial manufacture to when they are administered.  In the developed world, this is an established process as the infrastructure for distribution and storage is in place to maintain a temperature controlled supply line.  However, the developing world does not always have such infrastructure and additional effort must be made to ensure vaccines are kept at required temperatures.  In the process of transporting these critical medicines to and storing them in rural areas, reliable refrigeration is not available.  This may result in accidental freezing, high wastage rates or at worse failed vaccinations that can result in death.  These difficulties impact both cost and availability.  
To address this problem there has been an effort to develop thermostable vaccines.  VBI is advancing its LPV Platform that uses a formulation of synthetic lipids to suspend antigens and adjuvants and protect them from the damaging potential of moisture when it moves between a solid and a liquid.  In current formulations, proteins are suspended in water which holds the vaccine contents in solution until used.  However, when the expanding and contracting forces of the water come into play along with the heating and cooling of the solution, it can damage the proteins and render the vaccine useless.  

The LPV process may generate vaccines that do not need to be distributed through the cold chain thereby expanding their ability to be supplied worldwide and eliminate the costs, risks and burdens associated with cold chain handling.  VBI has tested its proprietary formulation and found that vaccines produced via the LPV process can maintain potency through temperature fluctuations between -20° to 40° Celsius in animal model testing. Their work is developing this technology in conjunction with Sanofi Pasteur and GlaxoSmithKline for new vaccines in development.  

This innovative approach to developing the next generation of vaccines has the potential to improve distribution, efficacy, and cost while reducing waste.  These benefits can go a long way toward improving immunizations in the developing world and improving the distribution of these valuable medicines.  

Public Offering

On October 25th VBI announced an underwritten public offering and a registered direct offering of its common shares.  The proceeds from the offerings will largely be used to advance the company’s three key programs: Phase III Sci-B-Vac, Phase I/IIa GBM and VBI-1501A in CMV.  The offering was priced at $3.05 per share for 14 million shares in the underwritten public offering and 6.8 million shares in the direct offering which will generate $63.5 million in gross proceeds.  There is a 30-day option for an additional 2.1 million shares also at $3.05, which may provide additional gross proceeds of $6.4 million.  

On October 31st VBI announced that it had closed the underwriting of 25.7 million shares and raised gross proceeds of $72 million.

Summary


VBI Vaccines has an impressive portfolio of vaccines based on two advanced technologies that can increase the efficacy, safety and distribution of the products in their pipeline.  The eVLP platform is able to use a structure that mimics the size and shape of a virus and includes viral antigens on the surface of its particle, but contains no viral RNA or DNA.  The LPV platform is equally exciting and has the potential to dramatically improve distribution of vaccines especially in developing countries as it eliminates the need for cold chain handling.  To fund these programs, VBI raised $72 million in gross proceeds last month.  These funds will support the launch of the Phase III program for Sci-B-Vac and support continued work on CMV, GBM and the other programs in the pipeline. 

SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR. 

DISCLOSURE: Zacks SCR has received compensation from the issuer directly or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks provides and Zacks receives quarterly payments totaling a maximum fee of $30,000 annually for these services. Full Disclaimer HERE.

 
User ID:
Password:
Remember my ID: