INOVIO - INO

Since I just bought some INO I figured I should spell out why I bought and what I expect.

It all centers around this VGX merger that is now proposed and underway. Inovio has an electroporation device which injects a vaccine into humans. VGX has the DNA vaccine which in mouse studies worked to provide 100% immunity against highly pathogenic H5N1 - avian flu:

1)
Inovio/VGX merger to expedite DNA vaccine development

By Gareth Macdonald

09-Jul-2008 - Electroporation specialist Inovio Biomedical Corp and vaccine developer VGX Pharmaceuticals believe that their recently announced merger will create a firm capable of rapidly moving DNA vaccine candidates from the laboratory to the clinic.

The definitive agreement, which has been approved by the boards of both firms but is still subject to clearance by stockholders, will integrate Inovio's electroporation technology with VGX's pipeline of developmental DNA vaccines and Cellectra delivery platform.

In January this year, BCC research forecast that the global market for therapeutic vaccines, which is valued at around $20bn (€12.7bn), will be worth $34bn by 2013, representing a compound annual growth rate of nearly 11 per cent.

While traditional antigen-based products will continue to dominate the sector, the benefits offered by DNA vaccines in terms of minimized side effect profile make any successful technology an attractive proposition.

"We are highly confident that the combined company will advance the potential of developing and delivering new DNA vaccines that could play a significant role in treating or even preventing diseases. Leadership of both companies could not forego this medical and market opportunity," commented Avtar Dhillon, Inovio Biomedical's CEO.

Joseph Kim, co-founder, president and CEO of VGX Pharmaceuticals, said that: "Significant, growing evidence indicates that electroporation has a pivotal role to play in enabling the potency of this promising new generation of vaccines and VGX has already made a strong commitment to this DNA delivery technology."

FDA accepts VGX's DNA cervical cancer vacc IND

Earlier this month, the US Food and Drug Administration (FDA) approved VGX's Investigational New Drug (IND) application for the DNA vaccine for cervical cancer, VGX-3100. Following the decision, the firm announced plans to initiate a Phase I clinical trial in the third quarter this year.

At present, the cervical cancer vaccine market is shared between Merck and Sanofi Pasteur's Gardasil and GlaxoSmithKline's (GSK) Cervarix. Both products are traditional antigen-based vaccines that incorporate a limited range of antigens present in the most commonly circulating human papilloma virus (HPV) strains.

In contrast, VGX-3100 is a DNA vaccine that has been designed to offer protection against a wide range of HPV viruses. The product was developed using VGX's SynCon DNA antigen platform, which aligns a selection of primary DNA sequences for each antigen and selects the base that is most common or relevant at each position using a series of sophisticated statistical algorithms.

The selected composite antigens are then included in the vaccine. VGX claims that the approach allows it to identify the DNA sequences that are most likely to elicit cross-reactive immunity to the widest range of HPV viruses, thereby providing enhanced immune protection.

Source

2)
Inovio Biomedical's First Proprietary DNA Vaccine Achieves 100% Protection Against Avian Flu in Pre-Clinical Testing

Wednesday July 16, 6:00 am ET

Results Suggest Experimental DNA Vaccine May Protect Against Multiple Seasonal and Pandemic Influenza Strains

SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO - News), a leader in enabling the development of DNA vaccines using a proprietary electroporation-based DNA delivery platform, announced today pre-clinical results from two proprietary plasmid DNA-based universal influenza vaccine candidates using the company’s proprietary electroporation delivery technology and, specifically, a new intradermal device. In this study, 100% of the immunized mice given a lethal challenge of highly pathogenic H5N1 influenza virus (A/Vietnam/1203/04) survived and showed only minor weight loss.

The DNA vaccine design was based on a different influenza strain (H1N1) than the influenza strain used in the challenge, providing evidence that a universal vaccine based on conserved genes common to multiple strains of seasonal influenza and even potential pandemic influenza may have the possibility to provide widespread protection against such viruses. In collaboration with Vandalia Research Inc., Inovio also tested the use of fully synthetic linear expressing cassettes (LEC) to express the same antigens and achieved similar results. These results were presented by Dr. Michael Fons, VP Corporate Development, on July 15^th at the Controlled Release Society 35th Annual Meeting and Exposition.

“We’re enthusiastic about these very early results because today’s strain-specific (homologous) influenza vaccines cannot provide universal protection against seasonal influenzas and potential pandemic influenza strains. Only a broad-spectrum (heterologous) influenza DNA vaccine, such as the one we’re testing, would have the potential to provide protection against multiple known and unknown influenza strains. Our hope is that such a universal vaccine may one day replace the standard seasonal vaccine and provide protection against the generally inconvenient symptoms as well as the more severe effects, including death, that can result from seasonal and pandemic influenzas,” said Inovio CEO Dr. Avtar Dhillon.

Current strain-specific influenza vaccines are designed to stimulate an immune response specific to a single influenza strain. Given that seasonal flu can rapidly mutate, such homologous vaccines may provide modest protection against variant influenza strains but cannot fully prevent the contagion from widely spreading and causing not only the familiar symptoms of the common cold but, in some cases, death. The major risk of pandemic influenza is that new virulent strains of influenza, such as the avian flu, which have never spread widely through a human population, would potentially result in harsher symptoms and widespread death because of the body’s delay in naturally building immunity to the virus and the inability to develop and distribute in a timely manner a vaccine specific to that influenza strain.

The concept of a universal broad-spectrum vaccine is based on emerging scientific knowledge that “conserved” regions of the influenza genome are not under dramatic selective pressure to mutate. These genes and the antigens they express are common across most strains of influenza. This creates the possibility to develop heterologous influenza vaccines without knowing the genetic make-up of a future influenza strain that may have the potential to, for example, migrate from animals to man and pose pandemic risk.

This pre-clinical work involved two other technology advancements Inovio has been developing or co-developing:

1) Fully synthetic linear expressing cassettes (LEC), or linear constructs, represent a new type of carrier mechanism for the genes that comprise a DNA vaccine. Numerous clinical studies have provided evidence that DNA plasmids are inexpensive, safe, and effective for delivering DNA vaccines. LECs are a next generation of synthetic DNA constructs that are easier, faster and cheaper to make, while providing equivalent utility.

2) Inovio has developed a multi-product line of electroporation devices that can provide different electroporation parameters in different types of tissue. This pre-clinical work used a new intradermal device intended to deliver a DNA vaccine into skin rather than muscle, the tissue type that is the focus of Inovio’s existing clinical studies. Delivering a vaccine into skin creates the potential for greater tolerability and would therefore make such a device more acceptable for prophylactic (preventive) vaccination.

About Inovio Biomedical Corporation

Inovio Biomedical (AMEX:INO - News) is focused on developing multiple DNA-based immunotherapies. Inovio is a leader in developing human applications of electroporation using brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical. Interim human data has shown that Inovio’s DNA delivery technology, which is protected by an extensive patent portfolio covering in vivo electroporation, can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio and VGX Pharmaceuticals have announced a proposed merger. More information is available at www.inovio.com.

Source

3)
Inovio says Tripep reported addnl. interim results from hepatitis C virus phase I/II clinical study - Quick Facts

06/30/2008 6:36AM - RTT News

(RTTNews) - Inovio Biomedical Corp. (INO) said Monday that its partner, Tripep AB, reported additional interim results from its ongoing phase I/II clinical study of its ChronVac-C therapeutic DNA vaccine, which is delivered using Inovio's electroporation-based DNA delivery system.

The preliminary results are from the first two patients in the intermediate dose group to complete treatment against hepatitis C virus infection. Samples taken before, during and after treatment showed that the viral levels in blood decreased up to 87% and 98%, respectively, during treatment. Simultaneous activation of the patients' T-cell responses to the hepatitis C virus was recorded in conjunction with the viral load reductions. Inovio's electroporation delivery technology is intended to enhance the potency of DNA vaccines against cancers and infectious diseases.

ChronVac-C is a therapeutic vaccine given to individuals already infected with the hepatitis C virus with the aim of clearing the infection from the liver by boosting the body's immune response against the virus.

For comments and feedback: contact editorial@rttnews.com

Source

4)

Why the merger?:

Commercialization
Vaccine: owned by VGX.
Delivery technology: owned by Inovio.
Source

That kinda says it all - all under one roof, now.

5)
What do I expect?

Great things - a single DNA vaccine for multiple viruses of the same family, concocted to avoid mutations.

6)
iHub Message Board
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Nanotechnology approach shows promise with vaccines

by Nathan Bomey | Ann Arbor Business Review

Thursday March 13, 2008, 3:37 AM

Robert Ramey
James Baker, founder of NanoBio.

Researchers have long believed that nanotechnology could one day target afflictions such as cold sores.

But University of Michigan scientists recently revealed two studies suggesting that nanoemulsion vaccines helped mice build up immunity to smallpox and HIV.

The technology, which is licensed through Ann Arbor-based firm NanoBio Corp., would use an oil-based emulsion administered through the nose rather than injecting patients using needles.

James Baker, director of the Michigan Nanotechnology Institute for Medicine and founder of NanoBio, said recent studies have indicated "that mucosal immunity may be very important in protecting individuals from AIDS."

In unrelated news, NanoBio announced that it may soon begin Phase 3 clinical trials on one of its topical lotions after getting positive clinical data and receiving a corresponding $10 million round of funding.

The firm, a spinout of the University of Michigan, has received an additional $10 million in equity funding from Perseus LLC - which has now contributed $30 million over the past 18 months to NanoBio. Perseus is a private equity investment firm with operations in New York City and Washington, D.C.

NanoBio recently said that Phase 2 clinical trial data on its topical lotion candidate NB-001 displayed positive indications that the therapy is ready for Phase 3 - the final stage before a drug reaches the market.

Company officials indicated that the firm would begin planning Phase 3 trials for NB-001 - a lotion that aims to treat cold sores using a nanotechnology-based lotion.
Baker recently spoke with Business Review reporter Nathan Bomey about the nanoemulsion studies. Excerpts:

Business Review: What was the key breakthrough in this news about the nanoemulsion vaccines?

Baker: We demonstrated that this (technology) can be used for almost any type of vaccine.

In addition, it can produce the type of immunity that's most desired for protection against viruses - that is cellular immunity that induces destruction of virally infected cells.

Have you known for quite some time that nanotechnology could eventually target HIV?

I think both of these vaccines are new in terms of how they are approached. No one has been able to produce a kill-virus smallpox vaccine before, and the uniqueness of the nanotechnology platform, I think, is very important to that.

The other thing was that recently there have been failures of a number of different AIDS vaccines. And also new evidence has come out that suggested that mucosal immunity may be very important in protecting individuals from AIDS. It makes sense.

So the fact that this vaccine produces not just cellular immunity but also mucosal immunity may make it more effective than some of the vaccines that have previously failed.

There are many different ideas about how to create a smallpox vaccine. What makes this one stand out?

The key here is that most of the applications we might use this vaccine in are really very different from what's going on with smallpox before.

There wasn't a risk with smallpox right now that justifies the risk of a live viral vaccine. So for things like a monkeypox outbreak or a suspected bioterrorism event, the risk of the vaccine may actually outweigh the risk from the event.

So having a vaccine that's safer than the current vaccine but is effective in preventing the infection if it were to occur is a really a change in the dynamic.

Talk about the market for nanotechnology-based technology. What is that market like right now?

Well the market is really wide open and there's a potential for incredible growth. We estimate that for some of the projects NanoBio is currently developing, they could be billion-dollar markets. NanoBio has at least three or four potential drugs for those markets. That gives you an idea of the potential for this technology.

What is the FDA approval process like for nanotechnology-based technology right now?

I think that it's essentially the same as any other vaccine, and we hope to be in people with at least one nanotechnology-based vaccine by the end of this year.

Has the FDA historically looked at nanotechnology suspiciously or do they see it as promising technology?

I think they see it as promising technology. Part of that's been because we've done our homework and we've made sure that anything we brought to the agency was well justified, and we've done appropriate efficacy and toxicity testing to justify their evaluation.

In the life sciences industry, we're seeing a lot of fragmentation with the big pharmas outsourcing a lot of their services. Do you think nanotechnology firms could be a target for acquisitions from the major pharmaceutical companies?

I think that's a good possibility. In some ways, it's been easier for them to evaluate traditional companies because they have milestones.

But for example, a company like NanoBio, which now has positive Phase 2 clinical trials, it (has) really breakthrough products based on nanotechnology (and) could easily be perceived as a takeover target.

Link to article

Contact Nathan Bomey at (734) 302-1725 or nathanb@mbusinessreview.com.

NanoBio - Nanoemulsion vaccines effective against HIV?

February 28th, 2008

Posted by Roland Piquepaille @ 10:10 am

Nanoemulsions are non-toxic lipid droplets approved for human consumption and common food substances that are defined as ‘Generally Recognized as Safe’ (GRAS) by the FDA. But they also can be used for medical applications. Researchers at the University of Michigan have developed nasal nanoemulsion vaccines for influenza which were successfully tested in animals in 2003. Now, the same team has shown that nanoemulsion vaccines are effective against smallpox and HIV — at least for mice. The scientists are using an oil-based emulsion placed in the nose instead of needles. It should take years before this technique could be approved for human usage, but it really looks promising. But read more…

You can see above how nanoemulsion particles enhance the immune response system. “Nanoemulsion particles lyse virus and incorporate viral antigens into their structure. The particles are then rapidly taken up by antigen presenting dendritic cells to enhance presentation to helper T-cells.” (Credit: NanoBio Corporation). Please note that “lysis refers to the death of a cell by breaking of the cellular membrane” (Credit: Lysis page on Wikipedia).

These research projects have been led by James Baker Jr., director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences (M-NIMBS) ans some members of his team including
Anna Bielinska, a Research Assistant Professor. For more information about this specific project, please read the Nanoemulsions page at M-NIMBS.

Here is a more detailed explanation of how nanoemulsions work. “The surface tension of the nanoparticles disrupts membranes and destroys microbes but does not harm most human cells due to their location within body tissues. Nanoemulsion vaccines are highly effective at penetrating the mucous membranes in the nose and initiating strong and protective types of immune response, Baker says. U-M researchers are also exploring nasal nanoemulsion vaccines to protect against bioterrorism agents and hepatitis B.”

The smallpox results could lead to an effective human vaccine against smallpox that is safer than the present live-vaccinia virus vaccine. “When the mice were exposed to live vaccinia virus to test the vaccine’s protective effect, all of them survived, while none of the unvaccinated control mice did. The researchers conclude that the nanoemulsion vaccinia vaccine offers protection equal to that of the existing vaccine, without the risk of using a live virus or the need for an inflammatory adjuvant such as alum hydroxide.”

Regarding a possible protection about HIV, the researchers said that “the HIV nanoemulsion vaccine tested in the noses of mice in the study represents ‘a different approach in the way it produces immunity and the type of immunity produced.’ Vaccines administered in the nose are also able to induce mucosal immunity in the genital mucosa. Evidence is growing that HIV virus can infect the mucosal immune system. ‘Therefore, developing mucosal immunity may be very important for protection against HIV,’ added Baker.”

The study about a nanoemulsion vaccine protecting from smallpox has been published in Clinical and Vaccine Immunology under the name “A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine” (February 2008, p. 348-358, Vol. 15, No. 2). Here is a link to the abstract.

The other study, about a vaccine showing immunity against HIV, has been published in AIDS Research and Human Retroviruses under the name “Nasal Immunization with a Recombinant HIV gp120 and Nanoemulsion Adjuvant Produces Th1 Polarized Responses and Neutralizing Antibodies to Primary HIV Type 1 Isolates” (Volume 24, Number 2, Pages 271-281, February 2008). Here are two links to the abstract and to the full paper (PDF format, 11 pages, 217 KB).

Finally, this technology about nanoemulsion vaccines is licensed to NanoBio Corporation, “an Ann Arbor-based biotech company which Baker founded in 2000 and in which he has a financial interest.” Here are some other sources of information from NanoBio Corporation.

• their latest news release, news release named “Nasal Vaccine for Smallpox Confers High Levels of Immunity without Safety Risks” (February 26, 2008)
• a page about how their NanoStat technology works
• and a page about Mucosal-Vaccines, from which the above illustration has been picked

Sources: University of Michigan Health System news release, February 26, 2008; and various websites

http://blogs.zdnet.com/emergingtech/?p=848

US patents link
EPO patents link

Cancer/Viruses/Immunity

Researchers have found that mice with a tumor treated with a viral cancer killer not only have the tumor cured but months later when injected with another tumor have the ability to fight off the tumor themselves - their immune system does so on its own, without any need for more virus cancer tumor killer.

Cancer Vaccine

The procedure used in this study triggered an immune response to cancer cells, which means that it could be used as a cancer vaccine to prevent recurrence.

"We show that if you kill tumor cells directly in the tumor itself, you can get a weak immunity against the tumor, but if you use this virus to kill tumor cells in the lymph nodes, you get a higher immunity against the tumor," Dr. Vile says.
Link


Makes me wonder if that same learning experience by the immune system would be in play with a viricide treatment for any particular virus such as those under development by Nanoviricides who have viricides which can kill viruses. Perhaps when a flu virus of a particular kind is killed by the viricide the immune system is trained, somehow, to fight off any future viral infection of that particular flu bug without the need for more viricide itself - in effect a vaccine is created in the first instance of treatment.

It is thus envisioned that a vaccine could be created in a healthy person by first giving them the viral infection - then treating it with the viricide, killing it off and thereby providing a long lasting immunity - a vaccination, in effect.

Refs:
John Bell
The promise of viral therapies
Scientists use virus to wipe out cancer cells