Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
don't be, I am not here for savvy investors, but to learn just like you are. The more information, the better informed to make decisions. There is never enough. A nice thank you would be appreciated.
Nothing and something. A person needs to be informed as much as possible of anything that can affect their study and future. We can not predict what will happen, which is why the IF, but being well informed can guide them towards the correct path. And when encountered with a decision to be made, they have a greater chance of making the correct choice.
That's exactly what Oncosec did when they listened to Dr. Pierce and made the choice to focus only on ImmunoPulse IL-12 to help nonresponders by using anti PD-1. Keep in mind, after 2014 there was another choice other than Keytruda, since three months later of that same year Opdivo was also approved.
When you are planning to put money on a bio company, which you are probably planning to do with Oncosec else you would not follow it this long, there is nothing to base the speculation. Therefore, it is best to understand what the industry is doing in reference to the company. Immunotherapy is new, and Dr. Pierce spoke about it years before it began. But he never mentioned electroporation IL-12 until now.
what value is there for a medical student to take out huge loans to study books that are irrelevant to their future practice and that won't guarantee how much money they will get in return.
let me rephrase it for you. The reason why the share price dropped so much is because the stock market measures time when there is no revenue. Don't forget that time is money. Many do not understand the science like Dr. Pierce does, so it is normal to wait for proof before putting hard earned money behind a company that is just staring to test its concept. But there is no need to reply by mocking a person who has done their own research.
so what is the difference between first, second and last line therapy? What line of therapy will EP IL-12 Keytruda be place 'if' results are really good?
do your own homework, just like Dr. Pierce did.
What’s new in IL-12? Combination!
Chris E Lawrence1*, Mark Rubinstein2, Zoya Gluzman-Poltorak1, Vladimir Vainstein1, Lena A Basile1
Abstract Presentation From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)
National Harbor, MD, USA. 4-8 November 2015
IL-12 is a heterodimeric, pro-inflammatory cytokine that enhances the cytotoxic activity of natural killer (NK) cells and cytotoxic CD8+ T-lymphocytes, and induces an IFN-dominated Th1 CD4+T-lymphocyte response. IL-12 as an immunotherapeutic agent administered subcutaneously in cancer patients has demonstrated clinical responses in melanoma, T cell lymphoma, non-Hodgkin’s lymphoma, and AIDS-related Kaposi sarcoma, but was never developed
further. Having elucidated novel hematological properties of IL-12, we are advancing our proprietary recombinant human IL-12 (NM-IL-12) for the treatmentof the Hematopoietic Syndrome of Acute Radiation Syndrome. In three clinical safety studies conducted in
over 200 healthy human volunteers, subcutaneous NM-IL-12 was well-tolerated. No adverse immune reactions or immunogenicity were observed.
We have now developed a novel clinical paradigm for the use of subcutaneously administered, low dose NMIL-12 combined with standard of care radiotherapy, chemotherapy, or immunotherapy for the treatment of cancer. The pleiotropic effects of IL-12 are expected to augment the mechanistic, anti-tumor effects of each of
these treatments.
In vitro NM-IL-12 stimulated primary human NK cell secretion of IFN-g and the cytotoxic lysis of leukemic
cells, and inhibited production of pro-angiogenic IL-17 in human peripheral blood mononuclear cells. In vivo, recombinant murine IL-12 (rMuIL-12) caused significant tumor growth inhibition following total body irradiation (625cGy) in syngeneic Lewis lung and EL4 lymphoma tumor models. In the same models, rMuIL-12 in combination with cyclophosphamide also caused significant tumor
growth inhibition. In the case of the non-immunogenic Lewis lung cancer model the combination of chemotherapy and IL-12 enhanced immunogenicity. In both tumor models, the antitumor effects of IL-12 were accompanied by rapid recovery of neutrophils, platelets and red blood cells, depressed by radiation or chemotherapy. This suggests an additional benefit of NM-IL-12 to cancer patients' myelosuppressed following radiation or chemotherapy. Preclinical evaluation of NM-IL-12 with radiation therapy and chemotherapy is now followed by evaluating combination immunotherapy. PD-1 blockade elicits potent anti-tumor immunity in a subset of melanoma patients. We have thus evaluated the combination of rMuIL-12 and anti-PD-1 antibody in a clinically relevant, syngeneic model of spontaneous, highly metastatic B16 mouse melanoma has been tested.
In summary we show that NM-IL-12 has excellent anti-tumor potential when used preclinically in combination with standard of care anti-cancer treatments, including radiation, chemotherapy and immunotherapy. NM-IL-12 is expected to contribute durable anti-tumor responses in the clinic through potent immunoactivation and anti-angiogenic effects, and to replenish blood cells, while being safe, well tolerated and non-immunogenic.
I will gladly answer all your questions if necessary, but the laugh before you asking makes it seem like sarcasm. Someone that has followed Oncosec for more than a year would know the answers offered by different forums or at company conferences, and should be part of the research necessary by anyone investing their time or money. More importantly when it comes to cancer, is knowing the difference between first and second line therapy or a last resort. For now, the study I referenced is of last resort. Also, don't get confused, if EP IL-12 with Keytruda can help some non responders, it's a given that responders will benefit as well.
Combination with IL-12 has already been tested with standard of care (first line therapy) in preclinical studies and results are positive. You can start the research yourself by reading my next post.
Speaking of deep science that is going on, this past weekend, researchers from the Fred Hutchinson Cancer Research Center presented unpublished results at the annual AAAS meeting. They tested generic CAR-T cells to patients who had late-stage leukemia and lymphoma that had exhausted other treatment options.
Researchers were shocked to find that 27 of the 29 leukemia patients went into complete remission and showed no more signs of the disease.
In the study, T cells were removed from patient’s blood and tweaked their genes to recognize the cancer cells that would otherwise slip by the immune system. The CAR-T cells were inserted back using a vector. In many previous studies the T cells ended up being less effective over time, either because the cells themselves become exhausted or because the cancer cells inhibit detection. Dr. Stanley Riddell, one of the researchers behind the trial, figured a way to increase the results.Many of the patients who were not expected to live for more than a few months are still alive now, three years after the trial started.
The results of this trial were different. In addition to the results from the leukemia patients, 19 of 30 lymphoma patients responded to the treatment as well, after just a single dose of CAR-T cells. “This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients,” Dr. Riddell said. But the treatment isn’t perfect quite yet. During the trial, seven patients developed cytokine release syndrome, a life-threatening inflammation that results when too many cancer cells are killed at once, and two of the patients died as a result.
While that might be acceptable risk for a last-ditch effort for patients with terminal cancer, such dramatic side effects wouldn’t be acceptable for patients with earlier stage or less lethal cancers.
The researchers don’t yet know the best dose for the treatment that wouldn’t cause such a strong reaction but would still get rid of the cancer, and they don’t know how long the patients will remain in remission.
The researchers have submitted a draft of their study to a journal and hope that it will be published soon so they can continue their work. The study is being sponsored by Juno and the trial has a termination date of 2023.
I can see how ImmunoPulse might come into play here, due to its reduction of toxicity and capabilities to synergize. I see it as a first line therapy that can assist every other therapy in helping those that do not respond.
Why could it not have been a buy? That many shares in so little time, when there are not many sellers, but plenty of sideline buyers.
The way it works is the market always looks for the next buyer with the ask price, if that does not work it goes to the bid. If you haven't notice, the bid keeps increasing.
Thanks, it is appreciated! I found some reading which supports what many have not realized. Oncosec is aiming for first line therapy in Cancer.
Dr. Pierce knew when he decided to take on ImmunoPulse IL-12, that electrochemo-gene theory had already being proven. In 2003 a clinical study showed how intratumoral delivery of Interleukin-12 gene and bleomycin synergistically induced therapeutic immunity when performed by means of electroporation. Although either both bleomycin alone or IL-12, significantly suppressed the tumors, the combination therapy drastically improved the results. It significantly prolonged the mean survival period, while Natural killer and T lymphocyte activities were markedly enhanced in the mice that received the chemo-gene therapy. More important, the study concluded that electroporation delivery of IL-12 and a chemotherapy drug elicits innate and adaptive anti melanoma responses.
Bleomycin is a type of chemotherapy drug which is used as first line chemotherapy regimen when tumors are in their beginning stage. In everyday practice, doctors look for other options and caution is taken when using agents like anti PD-1 or any other combination. Radiation is the option for localized disease, since toxicity and the cost of these agents prevent their use as first line therapy. Multiple new approaches are promising, but the future is in the use of combination treatment with standard chemotherapy which soon can become replaced by ImunoPulse IL-12.
now that's refreshing! It must have hit the floor already if you have lost track.
I am referring to trademarks that the company owns.
You can search their details on the following page:
https://trademarks.justia.com/search?q=Oncosec
To me it means that the company is planning to sell ImmunoPulse not only in the use of electroporation, but also as DNA compounds for medical research as well as pharmaceutical preparations that are comprised of DNA compounds for the treatment of tumors, which will add to Oncosec's pipeline.
Refreshing? The share price has been falling for a year and a half. Refreshing would be a positive.
It did not last because the job was not intended to, since Merlin was only helping with the electrical engineering aspect of the device. I have to correct my previous post. The catheter device itself is being worked by Rev.1, who is developing a tissue sensing and feedback control of electroporation pulse trains in order to attain optimal gene transfer and minimal electroporation-mediated tissue damage. Most likely, the electrical part of the job by Merlin was completed and Oncosec is getting closer to attaining a device to treat visceral tumors.
Dr. Pierce explained, “Taken together, these engineering advances can enable access and high-efficiency gene delivery to tumors throughout the body. This is key as we move forward in developing OncoSec’s pipeline of novel intratumoral therapies”.
“Our partnership with Rev.1 Engineering and internal bioengineering expertise have allowed OncoSec to enhance our ImmunoPulse platform and position the Company as a leader in gene electro-transfer technologies in cancer immunotherapy,” says Punit.
“We are also strengthening our intellectual property portfolio in the area of gene and drug delivery via electroporation to reach visceral tumors and enhance the uptake of therapeutic agents.”
Coincidently to that last statement, Oncosec last week attained an additional trademark for ImmunoPulse representing the good and services of DNA compounds for medical research, as well as pharmaceutical preparations that are comprised of DNA compounds for the treatment of tumors. Adding to the other ImmunoPulse trademark the company had for medical devices or therapy to treat disease by using electroporation to deliver agents to stimulate a systemic immune response.
8-k released today. Ernie, while you are trying to figure out why the share price dropped significantly for a year and a half, today a Termination of a Material Definitive Agreement with Merlin was informed to the SEC.
OncoSec and Merlin had entered into a Research and Development Services Agreement in March 2015. Under the Amended Agreement, Merlin has provided research and development services to Oncosec. They have developed a catheter device used to treat visceral tumors. After reviewing the cost and efficiency of its programs, Oncosec has terminated the Amended Agreement in a notice to Merlin dated January 21, 2016. The termination date will be effective February 21, 2016. Oncosec will now work with Merlin to transition Merlin’s projects in advance of the termination date. Expect news before the termination date on what $1.5 million in cost has given to Oncosec.
You are confused. There has been numerous paid contributors for SmallCap Network that have written articles on Oncosec.
However, at the end of their last article you will find the following:
Bryan Murphy is a paid contributor of the SmallCap Network. Bryan Murphy's personal holdings should be disclosed above. You can also view SmallCap Network's complete disclaimer and disclosure.
By law, if the contributor has shares of the company, it has to be stated at the end of the article. Also, if Oncosec was to pay for such advertisement, it has to be stated, else, the SEC would be knocking on their door.
From their disclosure:
"SmallCap Network also employs contributors to help us manage and moderate our growing community. Their primary purpose is to keep our forum running smoothly and informatively for the benefit of its Members. They perform a variety of tasks, including acting as virtual liaisons and publishing information and opinions on select public companies or on behalf of certain third parties who have hired SmallCap Network for various market awareness services. These contributors also contribute to the various discussions throughout our community. They are free to contribute, or not contribute, as they see fit.
Some SmallCap Network Contributors may have investments in the stocks they discuss. All SmallCap Network employees and contractors -- are required to publicly disclose their current individual stock holdings at the end of an article they've written and in the appropriate area when referencing or discussing a stock they own."
Basically, I could be a contributor to SmallCap Network and so can you.
I am not sure you are following the facts. Go into their page and find the QualityStocks clients:
•Agora Holdings, Inc. (AGHI)
•Alternet Systems, Inc. (ALYI)
•Avant Diagnostics, Inc. (AVDX)
•Cherubim Interests, Inc. (CHIT)
•Dominovas Energy Corp. (DNRG)
•FlexWeek (FXWK)
•Giggles N' Hugs, Inc. (GIGL)
•GTX Corp. (GTXO)
•International Stem Cell Corp. (ISCO)
•Latitude 360, Inc. (LATX)
•Lingo Media Corp. (LMDCF)
•Moxian, Inc. (MOXC)
•Oakridge Global Energy Solutions, Inc. (OGES)
•OurPet's Company (OPCO)
•Star Mountain Resources, Inc. (SMRS)
•View Systems, Inc. (VSYM)
Now, show me some facts that can support your statement.
Last week there were changes done in the TNBC study. Before a patient starts the TNBC trial, both estrogen receptors and progesterone receptors are tested. Different labs have different cutoff points for calling the cancer either hormone-receptor-positive or hormone-receptor-negative. For example, if less than 10% of the cells stain positive, one lab might call this a negative result. Another lab might consider this positive, even though it is a low result. Research studies have shown that even cancers with low numbers of hormone receptors may respond to hormonal therapy, which is what Oncosec is looking for with a low requirement of 5%. Since ER-negative tumors have 1 – 9% positive cells, the TNBC study has been modified to increase the percentage of cells staining, giving a range of 5-10%.
Therefore, the inclusion criteria has been expanded as follows:
*Treatment refractory disease is defined as the persistence of tumor lesions following at least one intervention that may include chemotherapy, radiation and/or surgery, or any combination thereof.
*Patients must have both ER and PR staining of 5% and be HER2-negative. Patients with ER or PR staining of 5-10%, but who have historically been treated as TNBC may also be enrolled.
*Patients must not have disease that, in the opinion of the investigator, is considered amenable to potentially curative treatment.
Notice from this last added inclusion that intratumoral plasmid IL-12 electroporation in patients with TNBC will be tested as a last line of therapy.
In addition, the non-vaccination requirement was changed to include patients who have been vaccinated against Hepatitis B and who are positive for ONLY the Hepatitis B surface antibody are permitted to participate in the study.
Coincidently, a recent study has shown high rate of Hepatitis B reactivation in Chinese patients receiving Rituximab (chemotherapy) for Lymphoma. It seems Oncosec is aiming to cover the higher demand, keeping in mind their Chinese patent.
Whoever prepared the study did not think through some details, and my guess is that it was done by the former CMO, Dr. Mai H. Le.
Just your opinion? why not rather give out some reasoning. Like for instance, another way the share price goes up is with positive results in studies, and that is not an opinion, it's a fact. Now, how long until that happens? not that long, since this year will be meaningful for Oncosec.
On January 22, the poster presentation Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors will be presented as poster. In the study sponsored by Plexxicon, Dr. S. Hu-Lieskovan and Dr. Antoni Ribas are both UCLA investigators in the clinical trial and Merck is providing the funding.
On October, 2015, Daiichi Sankyo and Plexxicon’s investigational CSF-1R Inhibitor Pexidartinib picked up the FDA's Breakthrough Therapy Designation for a Phase III cancer drug, putting it in line for preferential access to agency experts as it moves toward approval.
In March 2015, Drs. Ribas and Hu-Lieskovan found that a new triple combination therapy shows promising signs of more effectively controlling advanced melanoma than previous treatments and also with fewer side effects. In the new study led, by UCLA Jonsson Comprehensive Cancer Center, the scientists combined targeted therapies utilizing the BRAF inhibitor drug dabrafenib and the MEK inhibitor drug trametinib, with immunotherapy, which is treatment that uses a person’s own immune system to help fight cancer. Both drugs belong to GlaxoSmithKline.
Before that, on November 2014, Drs. Paul Tumeh and Antoni Ribas, colleagues at UCLA published results from an assay in demonstrating a strong correlation between the density of CD8+ T cells, located at the invasive edge of melanoma lesions, and the probability of response to Merck’s pembrolizumab. Using quantitative image analysis, Tumeh demonstrated that the number of CD8+ T cells/mm2 at the tumor margin was the feature most predictive of response and non-response to pembrolizumab. At the same time, both doctors began working in a preclinical collaboration between Plexxikon, UCLA and Oncosec, to test the combination of Plexxikon’s selective CSF-1R inhibitor pexidartinib(PLX3397) with OncoSec’s Immunopulse IL-12.
In addition, the 5th Inflammatory & Immunological Biomarkers Conference which will be one of the three conferences taking part at the Biomarker Summit 2016 to be held on March 21.
Dr. Tumeh will be speaking in the plenary session Novel Technologies in Biomarker Development. For more than a year, Dr. Tumeh has been helping PerkinElmer, UCLA and OncoSec on a collaboration to create a Patient-Selection Biomarker in Immunotherapy.
“Dr. Tumeh has demonstrated the potential of applying his highly quantitative approach to assessing the ‘stalled’ CD8+ lymphocytes, which are the key effector cells driving response to anti-PD-1 therapy. This work has the potential to identify responders from non-responders. Dr. Tumeh’s work, combined with PerkinElmer’s technology, may lead to the development of a critical diagnostic tool for identifying non-responders to anti-PD-1 monotherapy". Dr. Pierce.
A future combination study of Keytruda and ImmunoPulse IL-12 might be in the works.
Oncosec in May 2015 began a Sponsored Research Agreement with Massachusetts General Hospital. Under the agreement, researchers planned to evaluate ImmunoPulse IL-12, in a Human Papilloma Virus (HPV) tumour mouse model. Sara I. Pai, MD, PhD is serving as the principal investigator for the pre-clinical study. She is an expert in HPV-associated oropharyngeal cancer and has performed extensive research to better understand how cancer cells evade the immune system and how this process of immune evasion can be reversed.
"Intratumoural delivery of cytokines, such as IL-12, has the potential to alter the tumour microenvironment while minimizing the attendant systemic toxicity associated with other immunotherapeutic target delivery systems," said Dr. Pai.
In January 2016, Dr. Pai will begin enrollment for a phase 2 study that is sponsored by Massachusetts General Hospital with Merck as the collaborator. The tittle is Study of Anti-PD-1 Therapy for HPV-associated Recurrent Respiratory Papilloma Patients with Laryngeal, Tracheal and/or Pulmonary Involvement. The research will evaluate Pembrolizumab as a treatment for Recurrent Respiratory Papillomatosis. In patients who have RRP, virtually 100% of the time it's caused by HPV DNA. For that reason, mostly children and young adults are diagnosed with the disease.
It is not a device that Merck has patent, but rather a model that provides a platform for evaluating the efficacy of biomolecules engineered to enhance anti-tumor human immune responses. It is a plan based on the fact that there was cytotoxic activity that killed tumor cells and allowed 100% of the treated mice to survive, however, it does not mention if any toxicity was produced due to the over exposure to the cytokines.
According to Merck’s patent, “the targeted delivery of IL-12 to the tumor microenvironment represents a highly promising approach for tumor immunotherapy, because it could render the cytokine more effective and less toxic. Therefore, it is the major subject of this invention, to provide an effective and above all exercisable therapeutic cancer-immunotherapy approach by using the efficient antitumor immunity of the drug.” So far it has been studied with the use of radiotherapy and chemotherapy, but they still do not have a device.
The patent states, that “to maximize immunocytokine tolerability, the antibody selected as a vehicle must bind specifically to an antigen uniquely found in tumors. Antibodies directed against necrosis- associated antigens, which are abundantly present in tumors but not in normal tissues, offer an attractive delivery approach. One strategy for improving the safety of proinflammatory cytokines, such as IL-2 and IL-12, is to direct their delivery to tumors via fusion to a tumor-targeting antibody. Such antibody- cytokine fusion proteins, or "immunocytokines," have previously demonstrated the ability to enhance anti-tumor immunity in preclinical models”. Merck will still need to figure out a delivery system. Merck plans to use the engineering of novel immunocytokine formats that may help generate fusion proteins of acceptable pharmaceutical quality like, IL-7 or IL-2, for those proteins which do not lend themselves to a direct fusion with antibody fragments. It sounds risky because of the high toxicity IL-12 and every other cytokine might bring.
Oncosec is past the pre-clinical stage and are working on the approval of something that suddenly has the attention of Merck. ImmunoPulse has proven it will do a more efficient and safer job as a delivery device for any combination that requires IL-12, an important piece of the puzzle.
The authors concluded that without IL-12 treatment, the human cells infiltrating the RMS tumors were immature NK cells and HLA class II-negative M2 macrophages that were permissive for tumor proliferation. Treatment with IL-12 drove development of M1 pro-inflammatory macrophages and up-regulated several receptors on NK cells required for their functionally maturity and ability to secrete IFN-g and TNF. The combination of IL-12 and IL-7 suppressed tumor cell proliferation but did not promote the human cytotoxic immune cell responses. Combining IL-12 with IL-2 also led to tumor senescence, but the infiltrating T and NK cells demonstrated cytotoxic activity that killed tumor cells and allowed 100% of the treated mice to survive. The tumor-bearing humanized mouse provides an excellent platform for evaluating the efficacy of biomolecules engineered to enhance anti-tumor human immune responses.
Exactly what Dr. Pierce has been saying, now let's see what happens when combined with anti PD-1.
MERCK’S PATENT FOR CANCER-TARGETED IL-12 IMMUNOTHERAPY
International Application for patent was begun in Germany last year, preparing the field for what the future holds.
Abstract:
The invention is directed to cancer immunotherapy. The invention is specifically directed to the induction of innate or adaptive antitumor immunity initiated by the administration of targeted IL-12 molecules preferably in conjunction with IL-2 and / or IL-7 to a cancer patient, who suffers from cancer of the muscle, bone, nerves, cartilage, tendons, blood vessels, etc., preferably from sarcoma. The invention is specifically related to the use of IL-12 in form of the specific immunoglobulin cytokine fusion protein called NHS-IL12, preferably in combination with a form of IL-2 and / or IL-7 exhibiting prolonged pharmacokinetics for the treatment of said cancer diseases.
According to the invention, it is preferred to combine the administration of targeted IL-12, such as NHS-IL12, with IL-2 or IL-7, preferably with IL-2 and IL-7 in bound, fused or complex form as specified in detail above and below. The coadministration can be done simultaneously or sequentially, wherein in the latter case the immunomodulating agent can be administered hours or days before or after administration of the targeted IL-12 molecule like NHS-IL12, following a specific dose and time regimen.
According to the invention, it is principle possible to combine the administration of targeted IL-12, such as NHS-IL12 with radiotherapy and/ or chemotherapy.
According to the invention, said tumor-targeted IL-12 therapy is useful to cause cancer cell senescence, which is preferably generated by increased production of endogenous IFNy and / or TNF in succession of said stimulation or induction of the patient's immune system triggered by said targeted IL-12 therapy. It was found that by said treatment according to the invention the senescence of the cancer cells results in stable growth arrest. Furthermore it was found that the senescence of the cancer cells and tissue remission is independent on direct immune specific cytotoxic effects, such as generation and activation of NK-cells and macrophages, although these cells are triggered by IL-12.
According to the invention the tumor-targeted IL-12 therapy is useful in cancer
Historic National Coalition Formed to Accelerate Next Generation Immunotherapy in Cancer.
Today it was announced “the launch of The National Immunotherapy Coalition (NIC), a historic alliance--in collaboration with Independence Blue Cross, one of the nation’s largest payers and Bank of America, one of the largest self-insured companies in the U.S.--with a singular focus: accelerating the potential of combination immunotherapies as the next generation standard of care in patients with cancer.”
“This unprecedented collaboration of multinational pharmaceutical, biotechnology companies, academic centers and community oncologists will make possible access to over 60 novel and approved agents under exploration in the war against cancer and will enable rapid testing of novel immunotherapy combination protocols, forming the basis of The Cancer MoonShot 2020. The NIC will design, initiate and complete randomized clinical trials in cancer patients with cancer at all stages of disease in up to 20 tumor types in as many as 20,000 patients by the year 2020.”
Finally insurance companies are getting involved in cancer. The fastest and safest delivery system will benefit the most, for being the one to reduce costs.
Thanks Titan for sharing that article, it says a lot. The importance of being able to directly program a cell with the help of IL-12, into assisting the immune system.
The difference between ZIOP and Oncosec is in their delivery platform. Ziop uses an adenoviral vector to deliver a virus into the cell and instruct the production of the IL-12 cytokine.
“Adenoviruses are medium-sized (90–100 nm), nonenveloped (naked) icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome. There are over 51 different serotypes in humans, which are responsible for 5–10% of upper respiratory infections in children, and many infections in adults as well. When these viruses infect a host cell, they introduce their DNA molecule into the host. The genetic material of the adenoviruses is not incorporated (transient) into the host cell's genetic material. The DNA molecule is left free in the nucleus of the host cell, and the instructions in this extra DNA molecule are transcribed just like any other gene. The only difference is that these extra genes are not replicated when the cell is about to undergo cell division so the descendants of that cell will not have the extra gene. As a result, treatment with the adenovirus will require readministration in a growing cell population although the absence of integration into the host cell's genome should prevent the type of cancer seen in the SCID trials. This vector system has shown real promise in treating cancer and indeed the first gene therapy product (Gendicine) to be licensed is an adenovirus to treat cancer.”
Notice the major differences from the Immunopulse platform. For starters, the gene does not reproduce when the cell undergoes cell division, therefore therapy with the dangerous virus will be lengthy, with the risk of over producing IL-12. On the other hand, electroporation allows placing IL-12 as needed, directly into the cell and getting the job done faster while avoiding dealing with the problem of controlling the production of IL-12, but rather avoiding any toxicity from the interleukin. But the major difference that we should soon find out results on, is that Ziop’s therapy will work mainly on responders, while Oncosec’s can actually change the cell’s behavior and allowing the non-responder cells to be instructed.
Electroporation combined with Yervoy in Europe, not that unique.
Dr. Declan Soden, director of the Cork Cancer Research Centre, has worked in the area of targeted gene and drug delivery to tumours for the last decade. In that time his group has initiated 3 novel Phase I clinical trials, and currently over 350 patients have received a novel form of therapy for inoperable skin cancers. They have developed a device for the electroporation/permeabilisation of gastrointestinal tract cancers which facilitates a significant improvement in local drug or DNA absorption without the normally associated systemic side effects.
Currently the Cork Cancer Research Centre, is conducting a Phase ½ study for the treatment of malignant melanoma with electroporation to trigger immunological synergy with Ipilimumab. The start date was in September 2015.
Clinical Relevance
In a number of clinical studies (phase II and phase III) investigators have concluded that electrochemotherapy with bleomycin and cisplatin of cutaneous or subcutaneous metastasis or tumors has an objective response rate of more than 80 percent. Reduction of tumor size has been achieved with electrochemotherapy faster and more efficiently than in standard chemotherapy for both cutaneous and subcutaneous tumors. Electrochemotherapy involves combining a normally poorly absorbed chemotherapy agent and the delivery of an electrical field directly to the tumor.
The use of electrical pulses for cancer therapy has exciting potential applications beyond permeabilizing the tumor cell membrane.
The cell death mechanism induced by electrochemotherapy has been previously published to induce a type of immunogenic cell death, which helps in priming a strong local anticancer immune response.
Clinical studies are about to commence in Europe, looking to combine the immune priming effect of electrochemotherapy with newly available immunotherapeutic antibodies. Early indications have shown that this combination can be effective in generating a systemic tumor antigen specific cytotoxic T-cell response
It is a young company that is growing with no revenue and is at its lowest share price ever, while conducting their most important study.
I would pay more attention to the science and what the future might hold. Here is a recent publication relevant to the science.
Clinical Potential of Electroporation for Gene Therapy and DNA Vaccine Delivery
Published on December 2015 by the NCBI (National Center for Biotechnology Information)
ABSTRACT
Introduction: Electroporation allows efficient delivery of DNA into cells and tissues, thereby improving the expression of therapeutic or immunogenic proteins that are encoded by plasmid DNA. This simple and versatile method holds a great potential and could address unmet medical needs such as the prevention or treatment of many cancers or infectious diseases.
Areas covered: This review explores the electroporation mechanism and the parameters affecting its efficacy. An analysis of past and current clinical trials focused on DNA electroporation is presented. The pathologies addressed, the protocol used, the treatment outcome and the tolerability are highlighted. In addition, several of the possible optimization strategies for improving patient compliance and therapeutic efficacy are discussed such as plasmid design, use of genetic adjuvants for DNA vaccines, choice of appropriate delivery site and electrodes as well as pulse parameters.
Combinations of immunotherapies, like ipilimumab (Yervoy) with anti-PD-1 nivolumab (Opdivo), has shown a higher level of anti-melanoma activity than monotherapy with either nivolumab or ipilimumab, but is associated with increased toxicity. That is a problem that can be dealt with by using ImmunoPulse, while at the same time increasing IFN-y production by putting IL-12 in the mix, while at the same time helping the non-responders to the anti PD-1.
Bristol-Myers recently submitted a SBLA for the combination of Opdivo with Yervoy in advanced melanoma. The study application was granted priority review with a decision deadline of January 23, 2016. In the study, 945 patients with untreated unresectable or metastatic melanoma were randomized to receive nivolumab (n = 316), ipilimumab (n = 315), or nivolumab plus ipilimumab followed by nivolumab (n = 314). In this frontline study, approximately a third of patients were BRAF mutation-positive.
“You would give nivolumab first in the frontline setting followed by ipilimumab in nonresponders,” wrote Dr. Sznol, who sees potential for nivolumab to be used concurrently with ipilimumab. At the 2014 ASCO Annual Meeting he presented early-stage data demonstrating that the combination of nivolumab and ipilimumab nearly doubled median OS compared with either agent alone. “These data suggest that the concurrent administration of ipilimumab and nivolumab may be superior to sequential therapies.
“With recent data showing impressive clinical activity of PD-1 or PD-L1 antagonists in subgroups of patients with a variety of different cancers, the critical and foundational role of immune interventions in cancer treatment is no longer deniable,” wrote Mario Sznol, MD, Yale Cancer Center, in an editorial published in a January edition of The New England Journal of Medicine. IL-12 has been researched long enough to know it will take part in that role. Once Oncosec proves that EP IL-12 can ‘safely’ increase IFN-y production and subsequently increase expression of genes related to antigen processing and presentation TILs, including the expression of PD-L1, Oncosec will have the upper hand in whatever decision they make. Their platform can become a standard of therapy for all combinations. Keeping in mind that Opdivo and Keytruda are both humanized IgG4 antibodies that block PD-1. They will behave the same when combined with IL-12., so if ImmunoPulse is approved for one, it will be for the other as well.
BMS last week announced that a phase ½ combination study was initiated testing Opdivo with Adcetris for patients with CD30-expressing relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma, peripheral T-cell lymphoma and cutaneous T-cell lymphoma. Recent preclinical data suggest that Adcetris causes immunogenic cell death of tumor cells, providing rationale for combination with Opdivo, a human antibody that targets and inhibits the programmed death receptor-1 (PD-1), resulting in T-cell activation. Sounds very familiar to what Oncosec is trying to achieve with the use of IL-12, which is known as a T cell-stimulating factor and can stimulate the growth and function of T cells. Basically it stimulates the production of interferon-gamma.
The collaboration was announced on January of 2015 and just now it began enrollment. Notice that it took them 11 months vs 9 months that it took for the UCSF Oncosec collaboration to commence in their Phase 2b.
With Global IP Secured, ImmunID Outlines Plans for PCR-Based Cancer Companion Test Market
ImmunID announced this week it has obtained patent protection in China, adding to IP in Europe, Japan, and the US, and completing a global IP strategy protecting the firm's technology base. ImmunID is developing a method called ImmuneTracker for profiling T cell repertoires as a companion test for immune checkpoint inhibitors.
"Immunotherapy costs between $100,000 and $250,000 per patient, per year," Sixt said, but it is also "a real revolution in cancer; people for the first time are experiencing that you can effectively treat metastatic patients who are basically already written off according to usual wisdom, and some of them stand up and go home." The rate of full response, however, is around 4 percent to 20 percent, he noted, and "if you unleash the immune system, you get quite nasty side effects because the immune system is a very powerful beast — it can kill the cancer but it can also make a lot of trouble for the patient." Thus, success depends on predicting response and side-effects, Sixt said.
(I say, how about success depends on helping with response and side-effects?)
As a companion testing, there are numerous immune checkpoint inhibitors that might theoretically benefit from being guided by ImmunTracker data. As previously reported by GenomeWeb, AstraZeneca is developing the PD-L1 inhibitor MEDI4736; Roche/Genentech is developing MPDL3280A, a PD-L1 inhibitor; Bristol-Myers Squibb is advancing an anti-PD-L1 drug BMS-936559 and the PD-1 inhibitor Opdivo (nivolumab); and Merck is developing a PD-1 inhibitor Keytruda (pembrolizumab). The FDA recently approved Opdivo in advanced melanoma and advanced squamous NSCLC; and Keytruda in advanced melanoma. These four firms are studying these immunotherapies in NSCLC with the help of an IHC test from either Ventana or Dako. Perkin Elmer has also begun a collaboration with OncoSec to test its Vectra quantitative pathology imaging system as a means of determining responders to Keytruda.
GenomeWeb
yes it will, and we might get another hint soon, since in March 21, Dr. Tumeh will be speaking at the Global Technology Community meeting on Neurological Biomakers Summit. The plenary session is Novel Technologies in Biomarker Development. Dr. Tumeh has been helping PerkinElmer, UCLA and OncoSec on a collaboration to create a Patient-Selection Biomarker in Immunotherapy for almost a year.
Dr. Robert H. Pierce has previously stated: “Dr. Tumeh has demonstrated the potential of applying his highly quantitative approach to assessing the ‘stalled’ CD8+ lymphocytes, which are the key effector cells driving response to anti-PD-1 therapy. This work has the potential to identify responders from non-responders. Dr. Tumeh’s work, combined with PerkinElmer’s technology, may lead to the development of a critical diagnostic tool for identifying non-responders to anti-PD-1 monotherapy. We believe these non-responders may benefit from a combination approach of ImmunoPulse with checkpoint inhibitors, like anti-PD-1, where ImmunoPulse has the potential to convert non-responders to responders.”
GTCbio is a leading information center that provides quality forums, which facilitate the exchange of biopharmaceutical and biomedical intelligence between industry leaders, academic and government organizations, and the financial community. Our conferences cover a variety of topics, such as stem cell therapeutics, infectious diseases, biotech partnering, pharmaceutical litigation, government regulation, bio-based chemicals and many more. Founded in 2002, GTCbio stimulates scientific discussions, offers key business insights, and promotes partnering and deal-making in the ever-changing biotech and pharmaceutical world.
Punit might have unexpectedly given a hint of what’s to come in the following months, when interviewed.
"There is a ton of opportunities that we have in 2016 and beyond. I think where we are really focused on is this next year is going to be a pivotal year for clinical data highlighting this combination approach. One of the key trials that we have ongoing right now is a phase 2 clinical trial in metastatic melanoma with combining Keytruda, Merck’s anti PD-1, with ImmunoPulse IL-12. That trial is…we expect that patients are going to have a better clinical response than with Keytruda alone. In fact we are going after these patients that typically would not respond."
"Although Carter’s immune system, unlocked by Keytruda, is likely the main reason he is cancer-free, he undoubtedly benefited from the high-precision, high-intensity radiation he received to his brain, too. Carter said in August that he had “four spots of melanoma” in his brain, and received so-called stereotactic radiation therapy.
That “may have synergistic effects,” said Dr. John Suh, so that “the combination of stereotactic radiation and immuno-oncology drugs” is especially beneficial."
No one is expecting for the pps to increase due to that news. Why would it? What I am referring to is that president Carter was first administered Keytruda before beginning Stereotactic radiotherapy, which is a way of targeting radiotherapy very precisely at the tumour. You have the radiotherapy beams aimed at the tumour from many different directions around the head. That is almost similar to what Oncosec will be doing with Immunopulse in their combination trial, along with the incorporation of IL-12 that might also help with the non-responders.
not very persuasive for you to buy the stock, but sufficient to continue and increase the studies with over150 patients.
But if you are looking for data, I think there is plenty of data obtained from years of studying Interleukin 12 and cytokines.
The definition of Immunotherapy includes
• Giving you immune system components, such as man-made immune system proteins.
That's what ImmunoPulse will help to do. There is already data on the matter.
That's fair and understandable.
‘If a Man will begin with certainties, he will end in doubts; but if he will be content to begin with doubts he will end in certainties. It is only doubt that creates ’