TapImmune Inc. ("TapImmune" "TPIV") is a biotechnology company specializing in the development of innovative therapeutics and vaccines in the areas of oncology and infectious disease. TPIV technologies are based on an understanding of the function of a protein known as TAP. Transporters Associated with Antigen Processing (TAP) are proteins responsible for supplying tumor-associated antigens (markers) and viral antigens to the surface of infected cells.
These markers are required for the effective recognition and destruction of cancer cells and virus infected cells by the immune system. A wide variety of metastatic cancers evade destruction by the immune system due to absent or insufficient amounts of TAP, making the tumors unrecognizable. TPIV's lead product, the TAP vaccine performs a key step in moving characteristic markers called antigens to the surfaces of cells allowing the recognition and killing of cancer cells by the immune system. Without TAP, there are no cancer markers, so the immune system fails to spot the rogue cells and the cancerous cells can grow undetected.
Clinical studies to date have identified a large number of cancers deficient in TAP including but not limited to HPV related cancers such as melanoma, lung, prostate, breast and ovarian cancer. TapImmune believes these tumors would be responsive to the TAP therapeutic vaccine. In preclinical trials for melanoma and lung carcinoma, animal survival rates of 70% were achieved using TAP vaccine therapy and 100% survival when TAP was administered ex-vivo.
TPIV's vaccine has shown effective restoration of TAP and the TAP molecule also works as an adjuvant or to enhance targeted vaccines against infectious diseases. Including TAP in the much studied Smallpox Vaccine, its potency was increased by 100-1000 times. TPIV is currently developing models for the application of this technology for some of the most important societal pathogens. This is a new paradigm in the treatment of infectious disease and could significantly advance the development of new vaccines as well as improve those that already exist.
""Elegantly Simple’ Cancer and Infectious Disease Vaccine Uniquely Addresses Problems Found with Earlier Immunotherapy Approaches.....""
Seattle-based biotechnology innovator TapImmune Inc. is on to something ""Bigg — Very Bigg"". The company has engineered a remarkable, yet elegantly simple, way for the body to recognize tumour and infectious disease cells and provoke an aggressive immune response whereby the body’s own killer T-Cells attack and eradicate harmful foreign bodies. This with respect to any form of cancer or disease via a technology that’s entirely non-discriminate in helping the body eradicate dangerous cells of many kinds.
Underscoring the vast potential of TapImmune’s approach is its exclusive licensing option agreement with the Mayo Clinic for a breast cancer antigen technology complementary to the company’s TAP (AdhTAP) protocol. In a novel approach, TapImmune and the Mayo Clinic will co-develop a specialized vaccine for patients with very aggressive HER2/neu breast cancer. What’s unique is that TapImmune’s technology actually re-activates the body’s own immune system, triggering mission-critical self-curative mechanisms that would otherwise not function properly.
“We chose to work with the Mayo Clinic because they have great clinical expertise in breast cancer, and we’re focusing specifically on HER2/neu breast cancer because we found complementary technology with Mayo that will work with TAP and address the problems found with earlier approaches,” explains Dr. Glynn Wilson, chairman and CEO of TapImmune. “Importantly, we’re able to work with a leading expert on breast cancer vaccines, Dr Keith Knutson of the Mayo Clinic, who will conduct the trials. Through these trials, we’ll also address a huge clinical need for patients who express low to moderate levels of HER2/neu and are not candidates for treatment with Herceptin(R) (trastuzumab), an intravenously delivered monoclonal antibody.”
How it Works
Simply put, TAP (transporters associated with antigen processing) plays a major role in the complex human immune system. When foreign bodies (viruses and disease) attack cells in the body, the normal response is for killer T-cells to find those invaders and destroy them. TAP is a transporter that helps trigger an immune response by providing a pathway for tumour antigens to be expressed on the surface of the cell. In most solid cancers TAP levels are greatly reduced, which prevents the antigen presentation required to stimulate T-cells into action.
In the treatment of cancer, TAP is analogous to turning on the light bulb on the surface of tumour cells, allowing immune cells to “see” them and inspire action accordingly. For infectious disease treatment, TAP turns the light bulb to a higher intensity to prompt more immune cells to act.
TAP potentially allows the immune system to see everything that’s foreign on the surface, in contrast to other approaches that simply focus on a single tumour antigen to try and raise an immune response. Indeed, TapImmune’s technology is entirely unique in that it isn’t dependent on genetics such as other immunotherapies and doesn’t directly target the tumour cells, but instead assists the body’s own immune system to do what it was designed to do by turning the TAP back on and activating destroyer T-Cells into “kill” mode.
TAP and Breast Cancer
Wilson says with any vaccine, there are two requirements needed to create a good immune response: 1) stimulate the cytotoxic lymphocyte (Class 1 pathway) and 2) stimulate the pathway that stimulates the T helper cells (Class 2 pathway), which gives a long-lasting immune response. The failure to satisfy both of these requirements is one of the reasons other breast cancer vaccines haven’t progressed.
For breast cancer, we are developing a unique multicomponent vaccine that stimulates the Class 2 pathway (CD4 – helper cells) for a prolonged immune response and the Class 1 pathway (CD8 – cytotoxic T cells) to activate killer T-cells that will infiltrate and destroy tumour cells. The HER2/neu vaccines that had been tested in the past either do not stimulate sufficient cytotoxic T-cell response on the Class 1 pathway or they do not give a long-lasting effect. I realized that we have the capability here with the Mayo technology plus TAP of creating good responses on both sides of the immune system required for a good vaccine. It is a very innovative, creative and exciting approach.”
TapImmune President and CFO Denis Corin agrees: I think there are a lot of vaccine candidates that have gone through the mill and probably failed at Phase II or Phase III predominantly because the immune recognition and immune stimulation hasn’t been as effective as they needed it to be to come up with an end-level product. TAP is elegantly simple and we believe applicable across multiple types of cancers.
In the overall vision of the use of cancer vaccines, the ultimate goal is to have vaccines that can be used prophylactically at the earliest detection of pre-cancerous conditions such as DCIS, Corin continues. It is thought that the more advanced the cancer, the lower the TAP levels will be. TAP may be applicable to all stages of cancer if we consider experiments that treated smallpox, augmenting the normal levels of TAP and making a smallpox vaccine fully 100 to 1000-fold more potent.
The Science
The immune system distinguishes normal and cancerous (or virus-infected) cells by monitoring major histocompatibility complex (MHC) Class 1, a molecule on the cell’s surface. Nearly all cell types display MHC Class 1 antigen on their surface, continually providing information to the immune system. The MHC molecule, which contains small protein fragments (peptides), cycles to the surface of the cell to present foreign antigens to the cellular immune system, thereby activating the cytotoxic T-cells to kill virus-infected or cancerous cells.
In many cancers, there is a disruption in the process and the MHC on the cell surface is missing the tumour antigen peptides that identify the cell as being cancerous. They are basically hidden from the immune system and grow into tumours that eventually kill the person. Because TAP is affected negatively in the disease process, TapImmune’s vaccine technology turns TAP back on, supplying peptides to the MHC Class 1 molecule. TAP facilitates the binding of foreign peptides to the MHC Class 1 molecule. TAP facilitates the binding of foreign peptides to the MHC Class 1 complex, displaying them on the cell’s surface. Cytotoxic T-cells recognize them as foreign and ultimately neutralize and destroy abnormal cells.
Clinical studies on melanoma when examining primary and metastatic (spreading) tumours show a clear and significant correlation between TAP expression and survival.
The History and Future of TAP Technology
TapImmune (Formerly GeneMax...,Click Here To Check Out Vid On Former Genemax ) was formed in Vancouver, British Columbia, in the laboratories of immunologist Wilfred Jeffries, who with his colleagues produced exciting data showing that administration of TAP to replace deficient levels in tumours or augment natural levels in viral disease had significant therapeutic effects in animal models.
Four years ago, TapImmune principals acquired the technology and intellectual property outright from the university and set out to put together a board of directors and advisory board that understands the technology and its potential and to partner with credible collaborators like the Mayo Clinic and Aeras Global TB Vaccine Foundation, an organization largely funded by the Gates Foundation.
In discussions with Aeras Global TB Vaccine Foundation, we identified the potential of TAP for use in the joint development of their next-generation TB vaccine, said Denis Corin, TapImmune’s president and CFO. But you could also look at influenza, SARS, HIV, H1N1 and many other societal pathogens. We’re also working with Dr Poland and the Mayo Clinic on a new small pox vaccine. But, small pox is the tip of the iceberg. There are a number of nasty viruses that are potential bioterrorism threats and governments around the world could stockpile our TAP vaccine and call on it in the event of a bioterrorist threat.
<<Bigg Numbers Players>>
TapImmune’s TAP technology has the ability to complement most current immunotherapy approaches in a current estimated $21 billion market (Global Vaccine Market Outlook (2007–2010), Research & Markets). And, cancer vaccines will become a major player in the vaccine market, expected to be more than $8 billion by 2012.
A little known and young biotech company, Tapimmune (TPIV), is collaborating with the well-established, globally known Mayo Clinic, in Rochester, MN, to develop vaccines for breast cancer, which is expected to go into clinical studies early this year. The vaccine is expected to become a major therapy for breast cancer and other infectious diseases. Tapimmune and Mayo Clinic are also in a joint effort to come up with a vaccine for smallpox.
According to the American Cancer Society, an estimated 200,000 new cases of breast cancer were diagnosed in 2010. In 2009, Roche reported sales of $5 billion for Herceptin, an intravenously delivered monoclonal antibody for “HER-2” breast cancer. Tapimmune’s vaccine targets antigens on the HER-2 (human epidermal growth receptor 2) receptor that destroys cancer cells.
With its vaccine technology, Tapimmune expects to become a “world class immunotherapy company with products in multiple therapeutic areas in both cancer and infectious diseases,” says Dr. Glynn Wilson, Chairman and CEO of Tapimmune. “Our technology gives Tapimmune the potential to develop a new generation of safe and cost-effective vaccines for breast cancer and other infectious diseases,” he adds.
With the huge potential impact of its technology on such major diseases, early investors in the company believe Tapimmune’s stock is much undervalued, trading over-the-counter at a paltry 24 cents a share. They note that other emerging biotechnology companies in the same stage of product development that Tapimmune is in now has much higher market capitalizations.
Tapimmune’s novel technology uses the “Transport of Antigen Processing,” or TAP, to alert a human body’s immune system and jolt it into action to help destroy cancer cells. Roche’s Herceptin is primarily used in patients who express high levels of the antigen, or less than 50% of the population of patients afflicted with the HER-2 breast cancer. But combined with Tapimmune’s vaccine, it will improve HER-2’s efficacy in a larger population of patients who are immune to HER-2.So when the Roche product and Tapimmune’s vaccine are combined, a larger number of patients will benefit.
As such, Tapimmune believes the market potential for HER-2 vaccines that address a larger portion of breast cancer patients is significant and could grow revenues in that area to more than $15 billion.
A phase I clinical trial in breast cancer patients who have a form of the disease that expresses HER-2 receptors (also called HER-2/new breast cancer) is scheduled to be done at Mayo Clinic, with Dr. Kevin Knutson serving as principal investigator.
“Our business models are to advance multiple programs in cancer and infectious diseases into early clinical trials and to have corporate partnerships for larger clinical programs and marketing, says Dr. Wilson. Accordingly, Tapimmune plans to outsource all development and manufacturing activities to specialist organizations we collaborate with, he says.
Tapimmune expects to sign up multiple partnerships for technology development and commercialization in large markets because “our technology has the potential to improve a variety of other technologies and approaches--->(Expect Enormous News To This Effect Players) in the treatment of breast cancer and other infectious diseases, says Dr. Wilson. The company, he adds, expects to become a market leader in biotechnology “as we expect our continuing research to yield a pipeline of products.
Apart from a potential to make substantial returns from their investments, investors in the company should get the satisfaction that “their money would be directed to technologies which could alleviate pain and suffering caused by both the diseases and existing treatments.”
""When Tapimmune is recognized as an immunotherapy play along with the likes of Northwest BioTherapeutics (NWBO) and ImmunoCellular Therapeutics (IMUC), the market cap of Tapimmune is expected by some analysts to hit a market cap of $100 million, or a stock price of $1.50......""
<<Astronomical Numbers Players>>.....""Wake Up Wallstreet!..,We've Got a Winner~
After years in the lab, TapImmune (OTCBB:TPIV), the small biotechnology company developing immunotherapies, has finally announced their first FDA IND approval. Working with the Mayo Clinic, the firm will sponsor a Phase I HER-2/neu targeted therapeutic vaccine trial in HER-2/neu positive breast cancer patients.
The news is expected to be the first of several key news catalysts which will finally push the company's innovative TAP technology forward. TapImmune's Chairman and CEO, Dr Glynn Wilson, talks about this major milestone event for the company represents the first step in the development of a novel HER-2/neu vaccine that augments both CD4 Thelper cells and CD8 cytotoxic T-cells.
Question:
Dr Wilson, first of all, congratulations on your IND approval from the FDA and the research agreement with Mayo Clinic. We know this been a long journey for your unprecedented platform?
Dr. Glynn Wilson, Chairman and CEO: Thank you. We are tremendously excited about our progression into the clinic with the Mayo Clinic and are delighted to be working with a top-class clinical team there led by Dr. Keith Knutson and Dr. Amy Degnim.
Question:
Why is this milestone important for your TapImmune platform?
Dr. Glynn Wilson, Chairman and CEO: For any biotech company the entry into clinical development represents the culmination of significant research and preclinical development work that merits testing in humans. In this particular study it represents several years of research on the HER-2/neu technology at the Mayo Clinic and on TAP by TapImmune. For TapImmune it’s our first step into the clinical trial environment to test exciting product concepts and it represents a major milestone in our own corporate development and marks a new chapter for our stakeholders.
We believe deeply in the promise of our TAP technology and this HER-2/neu Mayo technology, and alone, or in combination we are very hopeful that this clinical program will result in a successful treatment and better the lives of many women and their families. The patient population for this vaccine is very broad. Broader than the current therapies and as such the opportunity to develop a vaccine that can expand the reach of treatment is very gratifying.
As far as market potential, the current treatment drug had sales of over $5Billion last year and we believe that ultimately this collaboration could significantly expand that market.
Question:
Can you give us a little more specifics on this trial?
Dr. Glynn Wilson, Chairman and CEO: The FDA has approved the Investigational New Drug Application (IND) that will allow Phase I studies on a therapeutic HER-2/neu vaccine trial in HER- 2/neu positive breast cancer patients. These studies will begin shortly (Q4, 2011) and will be conducted at the Mayo Clinic, Rochester, MN, under the direction of Keith Knutson, Ph.D., and Amy Degnim, MD.
In the trial, breast cancer patients that express the HER-2/neu antigen will be given the vaccine mixed with GMCSF as an adjuvant to enhance immunity. The trial aims to evaluate the safety of this vaccine as well as immune responses. This clinical program stems from a technology license option and sponsored research agreements between Mayo Clinic and TapImmune and is based on research on novel immunogenic peptide epitopes of the HER-2/neu antigen discovered in breast cancer patients with pre-existing immunity to HER-2/neu.
The ultimate aim of further clinical trials is to test this technology in synergy with TapImmune’s core TAP technology with the aim of producing a robust and long-acting immune response in a broad population of HER-2/neu positive breast cancer patients.
Question:
Can you clarify how TapImmune’s vaccine works and how it fits in with this trial or other possible vaccine candidates?
Dr. Glynn Wilson, Chairman and CEO: TAP, plays a key role in allowing the immune system to recognize tumor cells but in many tumors it is not functional. In preclinical studies it has been well established that restoring TAP into tumor cells and cancer- bearing animals can significantly improve the immune recognition of tumor-associated antigens. Collectively, these studies show that TAP1 gene transfer and expression of small amounts of TAP results in several critical effects:
(1) it restores the MHC Class 1 antigen-presenting pathway (2) it increases the number of tumour-infiltrating cytotoxic T-cells and dendritic cells (3) it enhances memory T-cell subpopulations, and (4) it improves animal survival
As these immune effects are central to the development of a successful cancer vaccine and are applicable to many solid tumors, the potential importance of using TAP expression in the immunotherapy of cancer was recognized and has provided the catalyst for conducting clinical studies.
We realized that our TAP technology was synergistic with a wide range of tumor antigen technologies. Our search for such antigens led to our collaboration with the Mayo Clinic. In our collaboration with the Mayo Clinic on this Her-2/neu breast cancer vaccine we will ultimately be combining AdhTAP1 with a Her-2/neu antigen technology in an approach to address earlier problems in the development of HER-2/neu vacacines, namely how to get a robust and longacting vaccine applicable to a large population of HER2/neu positive patients.
Question:
Just for a little more clarity on this type of Breast Cancer, what is Her2/neu?
Dr. Glynn Wilson, Chairman and CEO: HER-2/neu is a cancer antigen expressed in ~20% to 30% of breast and ovarian cancers. Herceptin (trastuzumab), a monoclonal antibody that targets the HER-2/neu receptor has become standard of care for patients with breast cancer. Annual sales of Herceptin are ~$5 Billion, however, approximately 70% of Her-2/neu positive patients will either not respond to or loose responsiveness to this drug.
Development of vaccine approaches against Her-2/neu antigens has been hampered by the ability to develop a robust cytotoxic T-cell response and a long-acting response due to stimulation of T-helper cells. In collaboration with investigators at the Mayo Clinic, TapImmune is addressing both of these deficiencies by evaluating technologies that can stimulate both CD8 and CD4 cells as a potential vaccine that we believe will greatly increase the responsiveness of this patient population.
With the World Health Organization’s recent vocal announcements of growing threats that multidrug-resistant and extensively drug-resistant forms of tuberculosis are spreading at an alarming rate in Europe, investors have once again begun to pay more attention to TPIV, which holds promise as both an anti-cancer and bio-defense play. TapImmune continues working with the likes of the Mayo Clinic and Aeras Foundation on vaccine candidates in both Cancer and Infectious Diseases.
For some time now, we've been telling readers that the company has been quietly building solid relationships within industry because of the relevance of the TAP technology and we continue to expect positive developments from the firm, particularly with Dr. Wilson on the verge of presenting data from the clinic on TAP levels and its affect on disease progression. There is plenty of evidence now from around the world that shows that TAP is indeed a key component in the antigen presentation process and where it is lacking or down regulated, disease progresses and prognosis is worse.
Reached for comment, Dr. Glynn Wilson stated: “One of the greatest problems facing our ability to respond to viral pandemics (e.g. bird flu, and bioterror threats of currently unknown origin) is how to be prepared for such possibilities. We envisage that our TAP approach could be widely applied and stockpiled independently so that it could be used alone or in concert with any vaccine antigens that might be available. Our work on smallpox and TB is only the starting point."
The Seattle based company’s TAP-based prophylactic vaccine- which initial tests indicate may increase the efficacy of targeted prophylactic vaccines by up to 1000 times- may significantly improve the efficacy of many current prophylactic vaccines and enhance the creation of new ones in the fight against many pandemic infectious diseases.
